Cryolipolysis devices and methods therefor

ABSTRACT

Described herein are cryolipolysis devices, systems, and methods for facilitating percutaneous access to a target blood vessel by performing cryolipolysis on subcutaneous adipose tissue obscuring the target blood vessel (e.g., a vessel used for hemodialysis treatment). Generally, the devices include a cooling member carrying a coolant that cools a selected portion of adipose tissue overlying the target blood vessel to reduce the selected portion of adipose tissue, thereby forming a depression in the adipose tissue and allowing the target blood vessel closer to the surface of the skin. In some variations, the cooling member is placed subcutaneously to directly cool the selected portion of adipose tissue. In other variations, the cooling member is placed external to the patient to indirectly cool the selected portion of adipose tissue through the skin.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.14/838,225, filed Aug. 27, 2015, which claims priority to U.S.Provisional Application Ser. No. 62/042,732, filed on Aug. 27, 2014,both of which are titled “CRYOLIPOLYSIS DEVICES AND METHODS THEREFOR,”and the contents of which are hereby incorporated by reference in theirentireties.

FIELD

The current invention relates to devices, systems, and methods forfacilitating percutaneous access to blood vessels.

BACKGROUND

Hemodialysis treatment involves obtaining access to blood through one ormore blood vessels. Specifically, one or more needles or catheters maybe inserted into one or more blood vessels to draw or retrieve fluid.Preferably, the one or more vessels may be located close to the surfaceof the skin. Frequently, a fistula may be formed between two vessels toprovide better access. A fistula allows blood to flow quickly betweenthe vessels, while bypassing the capillaries. The quality of thevascular access that may be achieved may impact the adequacy ofhemodialysis.

Typically, a vessel for vascular access (e.g., for hemodialysis) isideally located about 5 mm or less from the skin of the patient.However, some vessels may be too deep below the skin and an underlyinglayer of fat to reach with a conventional needle. In some cases, it maybe desirable to use one or more deep vessels whose access is obscured bya thicker layer of subcutaneous fat. As such, it may be desirable tohave devices, systems, and methods to facilitate percutaneous access tothese deep vessels.

BRIEF SUMMARY

Described herein are devices, systems, and methods for facilitatingpercutaneous access to blood vessels. In general, devices forfacilitating percutaneous access to a target blood vessel in a patientcomprises a subcutaneous probe to carry a coolant. The probe maycomprise an adipose tissue interface surface and a treatment segment.The treatment segment may define a delivery lumen extending at least thelength of the treatment segment to carry the coolant toward a distal endof the treatment segment and a return lumen to carry the coolant awayfrom the distal end of the treatment segment.

In some variations, the treatment segment overlies and is substantiallyaligned with a treatment portion of the target blood vessel. In anothervariation, the delivery lumen and the return lumen may be in fluidcommunication with one another at the distal end of the treatmentsegment. The distal end of the treatment segment may be blunt. At leasta portion of the delivery lumen and at least a portion of the returnlumen may be separated by a porous wall. The probe may further comprisea valve coupled to the return lumen to control a rate of a phasetransformation of the coolant across the porous wall.

In yet another variation, the delivery lumen and the return lumen may besubstantially parallel. The delivery lumen may be annular and surroundthe return lumen. The return lumen may be annular and surround thedelivery lumen. The delivery lumen and the return lumen may be laterallyoffset from one another. In some variations, at least one of thedelivery lumen and the return lumen is approximately semi-circular.

The device may include additional variations. The probe may comprise aproximal probe portion directed along a first axis, and the treatmentsegment may be directed along a second axis that is oriented at anonzero angle to the first axis. The adipose tissue interface surfacemay define at least one fenestration. A temperature sensor may becoupled to the treatment segment of the probe that measures at least oneof the temperature of the treatment segment and the temperature of thecoolant. The temperature sensor may be coupled to the distal end of thetreatment segment.

The probe may further comprise an adipose tissue agitator. An insulatormay be coupled to the probe. The insulator may be coupled to atranscutaneous segment of the probe. The insulator may be coupled to atleast a portion of the treatment segment of the probe. In someparticular variations, the probe may have an outer diameter of betweenapproximately 5 millimeters and 8 millimeters.

Also described here are systems for facilitating percutaneous access toa target blood vessel in a patient. In general, these systems comprise acooling device comprising a subcutaneous probe with an adipose tissueinterface surface and a treatment segment defining a fluidic channel tocarry a coolant. A cooling subsystem may be provided and comprises acooling mechanism and a fluid distributor. The cooling mechanismmodifies the temperature of the coolant, and the fluid distributordelivers coolant from the cooling mechanism at a flow rate into thefluidic channel of the probe.

These systems may include additional variations. The cooling mechanismmay comprise a closed fluidic system with a heat exchanger. The coolingmechanism may comprise a coolant reservoir in fluid communication withthe fluidic channel. The fluid distributor may comprise a pump. Thefluid distributor may comprise a wick.

In some variations, a control subsystem may be coupled to the coolingsubsystem to control at least one of the flow rate and the temperatureof the coolant. The probe may include a temperature sensor that measuresat least one of a temperature of the treatment segment of the probe andthe temperature of the coolant. The temperature sensor may be located onthe treatment segment.

In other variations, a guide member is provided to reposition the proberelative to a treatment portion of the target blood vessel. Each of theprobe and the guide member may comprise a magnet. In yet anothervariation, the system may comprise an adipose tissue agitator. Theadipose tissue agitator may agitate adipose tissue from a locationexternal to the patient. The adipose tissue agitator may be coupled tothe probe.

In yet further variations, the cooling device may comprise a sealingmember detachable to a proximal portion of the subcutaneous probe. Thecoolant may be a pressurized liquid coolant, and the fluid distributormay inject the liquid coolant into the subcutaneous probe. A proximalportion of the subcutaneous probe may be open-ended. The liquid coolantmay undergo a phase change and vent a vapor coolant from the proximalportion of the subcutaneous probe. The fluid distributor may comprise acoolant injector inserted into the subcutaneous probe to deliver thecoolant to the fluidic channel.

Also described here are devices for facilitating percutaneous access toa target blood vessel in a patient. In general, these devices comprise acooling member comprising a fluidic channel to carry a coolant. Thefluidic channel comprises a treatment segment to cool a selected portionof adipose tissue. A securing member may couple the cooling member to anexternal surface of the patient such that the treatment segment of thefluidic channel overlies and is substantially aligned with a treatmentportion of the target blood vessel.

In some variations of the devices, the fluidic channel may comprisetubing. A second cooling member may be provided and comprise a secondfluidic channel. The securing member may comprise a cuff. The coolingmember may be repositionable relative to the securing member. Thecooling member may comprise a sealing member detachable to a proximalportion of the cooling member.

In other variations, a tissue gatherer may be coupled to the coolingmember. The tissue gatherer may define a concave shape to hold tissue.The cooling member may be provided on an inner tissue interface surfaceof the tissue gatherer. At least one wire may actuate the tissuegatherer. A vacuum source may be coupled to the tissue gatherer.

Also described here are systems for facilitating percutaneous access toa target blood vessel in a patient generally comprising a cooling devicecomprising a cooling member comprising an elongate fluidic channel witha treatment segment to carry a coolant. A securing member may couple thecooling member to the skin of the patient such that the treatmentsegment of the fluidic channel overlies and is substantially alignedwith a treatment portion of the target blood vessel. A cooling subsystemmay comprise a cooling mechanism and a pump.

The cooling mechanism may modify the temperature of the coolant. Thepump may receive coolant from the cooling mechanism and deliver coolantat a flow rate into the fluidic channel of the cooling member. A controlsubsystem may be coupled to the cooling subsystem to control at leastone of the flow rate and the temperature of the coolant. In some ofthese variations, the cooling mechanism may comprise a closed fluidicsystem with a heat exchanger. The cooling mechanism may comprise acoolant reservoir in fluidic communication with the fluidic channel.

Also described here are methods of facilitating percutaneous access to atarget blood vessel in a patient. In general, these methods compriseinserting a subcutaneous probe into adipose tissue. The probe is alignedwith a treatment portion of the target blood vessel. A selected portionof adipose tissue surrounding the probe is cooled, thereby forming adepression in the selected portion of adipose tissue overlying thetreatment portion of the target blood vessel. In other variations, probeinsertion comprises inserting a distal end of the probe into the adiposetissue at a first location proximate the treatment portion of the targetblood vessel. Inserting the probe may further comprise passing thedistal end of the probe out of the adipose tissue at a second locationdifferent from the first location.

In some variations of these methods, cooling the selected portion ofadipose tissue comprises circulating a coolant in the probe. Circulatingthe coolant in the probe may comprise inducing turbulent flow of thecoolant. Circulating the coolant in the probe may comprise inducinglaminar flow of the coolant. Circulating the coolant in the probe maycomprise introducing a liquid coolant into a delivery lumen of theprobe. A temperature of the probe may be measured and at least one of aflow rate and a temperature of the coolant may be modulated based on themeasured temperature of the probe.

In further variations, circulating the coolant in the probe may compriseallowing the coolant to absorb heat from the selected portion of theadipose tissue and vaporize from a liquid coolant into a gaseouscoolant. Circulating the coolant in the probe may comprise allowing thegaseous coolant to enter a return lumen of the probe. Circulating thecoolant in the probe may comprise releasing the gaseous coolant from theprobe and controlling a rate of release of the gaseous coolant, therebycontrolling the rate at which the liquid coolant absorbs heat from theselected portion of the adipose tissue. Circulating the coolant in theprobe may comprise condensing the gaseous coolant from the return lumeninto the liquid coolant. Cooling the selected portion of the adiposetissue may comprise providing a solid or semi-solid coolant into theprobe and allowing the solid or semi-solid coolant to undergo a phasetransformation into a liquid or gas upon absorbing heat from theselected portion of the adipose tissue.

In other variations of the methods, the adipose tissue may behydrodissected. Hydrodissecting adipose tissue may comprise introducinga fluid into the adipose tissue. Introducing the fluid may compriseinjecting the fluid percutaneously. Introducing the fluid may compriseintroducing the fluid through the probe.

In yet other variations of the methods described, vasculature in a skinof the patient overlying the selected portion of the adipose tissue isvasoconstricted. Vasoconstricting vasculature may comprises applyingcold therapy to the skin of the patient overlying the selected portionof the adipose tissue. Vasoconstricting vasculature may compriseapplying a vasoconstricting substance to the skin of the patientoverlying the selected portion of the adipose tissue. Vasoconstrictingvasculature may comprise applying positive pressure to the skin of thepatient overlying the selected portion of the adipose tissue.Vasconstricting vasculature may comprise applying negative pressure tothe skin of the patient overlying the selected portion of the adiposetissue.

The methods may include additional variations. The adipose tissue may beagitated. Agitating the adipose tissue may comprise applying vibrationto the adipose tissue with a mechanical vibration source external to thepatient. Agitating the adipose tissue comprises applying vibration tothe adipose tissue with a mechanical vibration source internal to thepatient. Applying vibration to the adipose tissue with the mechanicalvibration source internal to the patient may comprise vibrating theprobe. Agitating the adipose tissue may comprise applying acousticvibration to the adipose tissue.

In yet further variations, cooling the selected portion of the adiposetissue comprises allowing dermis of the patient overlying the depressionto lie within approximately 5 millimeters from the treatment portion ofthe target blood vessel. Cooling the selected portion of the adiposetissue may be performed repeatedly during a treatment period comprisingat least seven days. Cooling the selected portion of the adipose tissuecomprises forming a depression that is between approximately 10millimeters and 40 millimeters deep. Cooling the selected portion of theadipose tissue comprises forming a depression that is betweenapproximately 80 millimeters and 120 millimeters long. The target bloodvessel may be at least one of the basilic vein and the cephalic vein.Coolant provided within the subcutaneous probe may be exchanged withanother coolant.

Some variations of these methods may comprise sealing a proximal portionof the subcutaneous probe with a sealing member. The coolant may beinjected in the subcutaneous probe continuously or periodically. Thecoolant having undergone a phase change from the probe may be removed.

Also described here are methods of facilitating percutaneous access to atarget blood vessel in a patient, generally comprising providing acooling member comprising a fluidic channel. The fluidic channel may bealigned with a treatment portion of the target blood vessel. The coolingmember may be coupled to an external surface of the patient. A selectedportion of adipose tissue overlying the treatment portion of the targetblood vessel may be cooled, thereby forming a depression in the selectedportion of the adipose tissue. In some variations, cooling the selectedportion of the adipose tissue may comprise circulating a coolant in theprobe. A temperature of the probe may be measured and at least one of aflow rate and a temperature of the coolant may be modulated based on themeasured temperature of the probe.

Some variations of these methods may comprise hydrodissecting theadipose tissue. The adipose tissue may be agitated. Vasculature of theskin of the patient overlying the selected portion of adipose tissue maybe vasoconstricted. Cooling the selected portion of the adipose tissuemay comprise allowing dermis of the patient overlying the depression tolie within approximately 5 millimeters from the treatment portion of thetarget blood vessel.

In yet other variations, a second fluidic channel may be provided. Thesecond fluidic channel may be aligned to a treatment portion of a secondtarget blood vessel. A second selected portion of the adipose tissueoverlying the treatment portion of the second target blood vessel may becooled, thereby forming a second depression in the second selectedportion of the adipose tissue. In another variation, the target bloodvessel may comprise at least one of the basilic vein and the cephalicvein.

Further described here are methods of facilitating percutaneous accessto a target blood vessel in a patient, generally comprising positioninga cooling member proximate to adipose tissue. The cooling member isaligned with a treatment portion of the target blood vessel.Cryolipolysis is performed on a selected portion of the adipose tissueadjacent the cooling member, thereby forming a depression in theselected portion of the adipose tissue overlying the treatment portionof the target blood vessel.

In other variations of the methods described, cooling the selectedportion of the adipose tissue may comprise circulating a coolant intothe cooling member. A temperature of the cooling member may be measuredand at least one of a flow rate and a temperature of the coolant ismodulated based on the measured temperature of the cooling member.Positioning the cooling member may comprise inserting a subcutaneousprobe into the selected portion of the adipose tissue. In anothervariation, positioning the cooling member may comprise coupling afluidic channel to an external surface of that patient overlying theselected portion of the adipose tissue.

Also described here are methods of facilitating percutaneous access to atarget blood vessel in a patient, generally comprising forming a fistulain an arm of the patient. A subcutaneous probe may be inserted intoadipose tissue overlying the target vein. The probe may be aligned witha treatment portion of the target vein. A selected portion of adiposetissue surrounding the probe may be cooled, thereby forming a depressionin the selected portion of adipose tissue overlying the treatmentportion of the target vein.

In some variations of these methods, the fistula may be abrachio-basilic fistula. The target vein may be a basilic vein. The armmay be dissected to provide access to the adipose tissue overlying thetarget vein. The alignment of the inserted subcutaneous probe may beverified by one of fluoroscopy and ultrasound. One of local anesthesia,general anesthesia or a brachial plexus block may be applied prior toforming the fistula. Hemodialysis treatment may be performed using thetarget vein. The probe may comprise a length of at least 8 mm, adiameter of 5 mm and a blunt distal portion. The probe may be insertedat a depth of 8 mm through a skin of the patient for the adipose tissueof 16 mm thickness. Cooling may be performed for 30 minutes at atemperature of 30° F.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustrative block diagram of a system for facilitatingpercutaneous access to blood vessels.

FIG. 2 depicts one variation of a system for facilitating percutaneousaccess to blood vessels with an internal cooling device.

FIGS. 3A and 3B depict two variations of an internal cooling device.

FIG. 4 is an illustrative depiction of a depression in adipose tissueoverlying a target blood vessel.

FIG. 5A depict another variation of an internal cooling device. FIG. 5Bis a cross-sectional view of the device in FIG. 5A.

FIGS. 6A-6H depict cross-sectional views of delivery and return lumensof variations of an internal cooling device.

FIG. 7A depicts another variation of an internal cooling device with atemperature sensor. FIGS. 7B and 7C depict alternative cross-sectionalviews taken along line A-A of the internal cooling device depicted inFIG. 7A.

FIGS. 8A-8C and 9 depict additional variations of an internal coolingdevice with coolant that undergoes phase change. FIG. 8B is across-sectional view taken along line B-B of the device in FIG. 8A.

FIGS. 10A and 10B depict variations of a cooling subsystem.

FIG. 11 depicts an illustrative block diagram of a control subsystem.

FIGS. 12A-12D depict variations of vasoconstrictors for vasoconstrictingvasculature of the skin.

FIGS. 13A and 13B depict variations of hydrodissectors forhydrodissecting adipose tissue.

FIG. 14 depicts a variation of an adipose tissue agitator for agitatingadipose tissue.

FIGS. 15A and 15B depict variations of guide members. FIG. 15C depicts avariation of imaging markers.

FIGS. 16A and 16B depict variations of insulation for use with thedevices described herein.

FIG. 17 depicts one variation of a system for facilitating percutaneousaccess to blood vessels with an external cooling device.

FIGS. 18A-18C depict variations of a securing member. FIG. 18D depicts avariation of an external cooling device to be used with one of morevariations of a securing member.

FIG. 19 depicts another variation of an external cooling device andanother variation of a securing member.

FIGS. 20A and 20B depict cross-sectional and perspective views,respectively, of a portion of a variation of a tissue gathering device.

FIGS. 21A and 21B depict side and perspective views, respectively, of aportion of another variation of a tissue gathering device.

FIGS. 22A and 22B depict two variations of an internal cooling member.

FIG. 23 is an illustrative depiction of at least a portion of thevascular anatomy of an arm of a human.

DETAILED DESCRIPTION

Generally described here are devices, systems and methods forfacilitating access to blood vessels, such as vessels for use inhemodialysis treatment. More particularly, described herein are devices,systems, and methods for facilitating percutaneous access to vesselsthat are obscured by a layer of subcutaneous fat. In some variations,the devices, systems, and methods described herein may improve access tofistulas formed using vessels having a deeper anatomical location thantarget sites for conventional surgical fistula-forming techniques (e.g.,they may improve access to fistulas formed between an ulnar artery and adeep ulnar vein, using the methods described in U.S. patent applicationSer. No. 14/052,477, filed Oct. 11, 2013, and titled “Devices andMethods for Fistula Formation,” the entirety of which is herebyincorporated by reference).

Additionally or alternatively, the devices, systems, and methodsdescribed herein may improve access at other fistula sites, such astraditionally desirable target sites for conventional surgicalfistula-forming techniques (e.g., radial artery-radial vein fistulas,certain fistulas in the legs). Access may be facilitated using a form ofcryolipolysis. Generally speaking, cryolipolysis involves cooling oftissue to preferentially induce cell death of fat cells. When tissue iscooled, certain cells (e.g., skin cells) may be less sensitive to cold,and thus may remain intact following this exposure to cold, while fatcells may undergo localized cell death when cooled to the sametemperatures, which may ultimately lead to reduction of the fatty tissuelayer. As a result of extended and/or repeated exposure to cold, thereduction of fat between the skin and blood vessels may increasepercutaneous access to the blood vessels.

Devices

Devices for facilitating percutaneous access to a target blood vesselinclude a cooling member that is placed proximate to a treatment portionof the target blood vessel to be used for vascular access (e.g., aportion of the basilic vein or cephalic vein to be used forhemodialysis). The cooling member cools a selected portion of adiposetissue overlying the treatment portion of the target blood vessel. Thiscooling may cause a reduction in volume of adipose tissue between thetreatment portion of the target blood vessel and the skin of thepatient. This may form a depression in the adipose tissue. As such, thesurface of the skin may be able to lie closer to the treatment portionof the target blood vessel, improving percutaneous access to thetreatment portion of the target blood vessel. As further describedbelow, in some variations, the cooling member is subcutaneous and isplaced internal to the patient in direct contact with adipose tissue. Inother variations, the cooling member is external and placed over theskin of the patient to indirectly cool a selected portion of adiposetissue through the skin. In yet other variations, the devices mayinclude any suitable combination of internal and external coolingmembers.

Some variations of the device include just the internal or externalcooling member, while other variations of the device include an internaland/or external cooling member coupled to one or more additionalelements. For example, in some variations, a cooling subsystem iscoupled to the cooling member via delivery and return lumens to maintaina desired temperature of the cooling member using recirculating coolant.In other variations, a control subsystem may be further coupled to thecooling subsystem to control the flow rate and/or temperature of thecoolant. In yet further variations, additional components such as aninsulator, securing member vasoconstrictor, hydrodissector, tissueagitator and tissue gatherer may be coupled to the cooling member tofurther aid in improving patient outcomes.

As shown in the block diagram of FIG. 1, in some variations, a coolingdevice 100 for facilitating percutaneous access to a target blood vesselin a patient 101 includes a cooling member 110 placed proximate to atreatment portion of a target blood vessel of a patient 101, eitherexternal to the skin or subcutaneously. The cooling member 110 may becoupled to a cooling subsystem 120 via a delivery lumen 130 and a returnlumen 132. The cooling subsystem 100 may include a coolant 122 formaintaining a desired temperature of the cooling member 110. The coolingsubsystem 120 may control the rate and type of flow of the coolant 122through the lumens 130/132 and cooling member 110 via a controlsubsystem 150 that receives one or more temperature measurements from atemperature sensor 112. In certain variations, the cooling device 100includes only a subset of the components illustrated in FIG. 1. Forexample, the cooling device 100 may include just cooling member 110,coolant 122 and temperature sensor 112, and not include coolingsubsystem 120, control subsystem 150, delivery and return lumens 130,132 and so forth.

Internal Cooling Devices

As shown in FIG. 2, in some variations, an internal cooling device forfacilitating percutaneous access to a target blood vessel in a patientincludes a subcutaneous probe 210 that carries a coolant. In somevariations, as described further below, the coolant is a fluid such as aliquid or gas, but in other variations, the coolant may be a solid or asemi-solid, such as a gel. The probe may be inserted subcutaneously tocool the adipose tissue between the target blood vessel and the skin ofthe patient. The probe may include an adipose tissue interface surfaceand a treatment segment for cooling a selected portion of adiposetissue. In some variations, the internal cooling device may be part of asystem 200 that further includes a cooling subsystem 220 with a coolingmechanism that modifies the temperature of the coolant and a fluiddistributor that receives coolant from the cooling mechanism anddelivers coolant to the probe. In some variations, the system mayfurther include a control subsystem 250 that controls the flow rateand/or temperature of the coolant.

Probe

A subcutaneous probe may include a treatment segment that may beinserted into adipose tissue in a variety of manners. For example, insome variations, as shown in FIG. 3A, the distal end of the probe may belocated within adipose tissue. A treatment segment 310 a of the probe310 may be inserted through patient skin 50 into a selected portion ofadipose tissue 52 overlying the target blood vessel 60. In somevariations, the distal end of the probe may be located external to thepatient. Probe 310 may include a proximal portion 310 b overlaid with aninsulator 360. Additionally or alternatively, the insulator may beprovided on any desired portion of the probe 310 such as a portion ofthe treatment segment 310 a of the probe.

The treatment segment 310 a of the probe may be located at a distal endof the probe, and may be configured to allow the treatment segment ofthe probe to be inserted into the tissue such that it is generallyparallel to the skin. In some variations, the treatment segment of theprobe may be oriented at a non-zero angle relative to the rest of theprobe body. For example, as shown in FIG. 3A, a proximal portion of theprobe 310 b may be oriented along a first axis, and the distal treatmentsegment 310 a of the probe may be oriented along a second axis that isat a nonzero angle to the first axis. The proximal portion 310 b mayinclude an insulator 360 that helps maintain a temperature of a coolantprior to circulation through the distal treatment segment. The proximalportion 310 b and the treatment segment 310 a of the probe 310 may joinat a vertex, a curved bend, or in any suitable manner. Alternatively,the treatment segment 310 a of the probe 310 may be located at a distalend of the probe and aligned with the rest of the probe body 310 b. Insome variations, as shown in FIG. 3B, the treatment segment 310 a of theprobe may be any suitable segment of the probe, such as a straightmedial portion of the probe.

As shown in FIG. 3B, the probe 310 a may be inserted through a firstlocation 51 of patient skin 50 on one end of the adipose tissue 52 andcontinue to pass through tissue 52 to exit through a second location 53of patient skin 50. In these and other variations, at least a portion ofthe external surface of probe 310 (i.e., the adipose tissue interfacesurface) may be in contact with and may cool the adipose tissue 52.

As shown in FIG. 4, when this cooling process is maintained or repeatedover a sufficient treatment period, as described in more detail herein,the selected portion of adipose tissue 52 overlying the target vessel 60may be reduced, which may result in a depression 70 or “trench” in theadipose tissue 52 and skin 50. Beneath the depression 70, the targetblood vessel 60 may be closer to the surface of the skin 50 than beforetreatment, thereby facilitating improved percutaneous access to thetarget blood vessel 60 in the region of the depression 70.

In some variations, the distal end of the treatment segment 310 a may beblunt and atraumatic. This may reduce the risk of puncturing the targetvessel with the probe 310. For example, the distal end of the treatmentsegment 310 a may be blunt (e.g., may have semispherical or otherrounded shape) in variations similar to that depicted in FIG. 3A inwhich the treatment segment 310 a is at a distal end of the probe.However, in other variations the distal end of the treatment segment 310a may have a sharpened tip or other suitable tip.

The treatment segment 310 a of the probe may be shaped similarly to thetarget blood vessel, particularly a treatment portion of the bloodvessel 60 to which easier access is desired. In some variations, thetreatment segment 310 a of the probe 310 may be shaped such that wheninserted into adipose tissue 52 between the skin 50 and the targetvessel 60, the treatment segment 310 a of the probe may be approximatelyaligned with and parallel to the treatment portion of the target vessel60. For example, as shown in FIG. 3A, the treatment segment 310 a of theprobe 310 may be generally straight, in order to track a straighttreatment portion of a target vessel. In other examples, the treatmentsegment of the probe may be curved in order to track a curved treatmentportion of a target vessel, or may have any other suitable shape.

Generally, the probes described here may be configured to allow tissue52 to be cooled for a sustained period of time. In order to do so, insome variations the probe may be configured to circulate a coolant. Inthese variations, the systems described here may comprise a temperaturesensor and a cooling subsystem to achieve a desired temperature ortemperatures, though they need not. In some variations, the probe mayinclude a fluidic channel for carrying coolant. As shown in FIG. 1, forexample, the fluidic channel may include a delivery lumen that carriesthe coolant toward a distal end of the treatment segment of the probeand a return lumen to carry the coolant away from the distal end of thetreatment segment of the probe. In some variations, the delivery lumenand/or return lumen may extend at least substantially along the lengthof the treatment segment of the probe. In other variations, the deliverylumen and/or return lumen may additionally or alternatively extend alongany other suitable portion of the probe or separate fluidic components.In some variations, the delivery lumen and/or return lumen may beapproximately parallel and/or adjacent to one another along at leastpart of their lengths along the probe. However, the delivery and returnlumens may carry coolant to and from the treatment segment of the probein diverging directions, or in any suitable manner.

In some variations, the delivery lumen and the return lumen may beseparate lumens that are in fluid communication with one another, suchas at the distal end of the treatment segment. For example, as shown inFIGS. 5A and 5B, the delivery lumen 514 extends centrally along the bodyof the probe 510 and carries a fluid coolant 570 toward the treatmentsegment located at the distal end of the probe 510. The return lumen 516is annular and concentric around delivery lumen 514, and receivescoolant 570 from the treatment segment at the distal end of the probe510 with coolant 570 flowing in the return lumen 516 in an oppositedirection than in the delivery lumen 514. Alternatively, a deliverylumen 514 may be annular and concentric around a return lumen 516 thatextends centrally along the body of the probe 510. The probe 510 mayinclude additional structural features, such as one or more support fins582, which may help maintain the shape of delivery lumen 514 and/orreturn lumen 516 for coolant flow.

In other examples, the probe may include any suitable arrangement ofmultiple lumens that may vary in shape, size, and number, such as thoseshown in FIGS. 6A-6G. The probe may include multiple delivery lumens 614and multiple return lumens 616, as shown in an exemplary configurationin FIG. 6A. The ratio of the number of delivery lumens to the number ofreturn lumens in the probe may be a ratio other than 1:1. For example,the probe may have two outer return lumens 616 and one central deliverylumen 614 as shown in FIG. 6B, or alternatively two outer deliverylumens and one central return lumen, or delivery and return lumens inany other suitable ratio. The delivery lumen 614 and return lumen 616may have complementary cross-sections, such as approximatelysemi-circular with similar arc lengths (FIG. 6C) or unequal arc lengths(FIG. 6D).

Additionally, in some variations, the probe, delivery lumen, and/orreturn lumen may have a non-circular overall profile. For example, theoverall profile of the probe may circumscribe a delivery lumen 614 and areturn lumen 616 that are adjacent and laterally offset from oneanother, such as the probe of FIG. 6E that encloses two circular lumensor the probe of FIG. 6F that encloses two rectangular lumens. As anotherexample, the probe may surround, but not closely circumscribe, adelivery lumen 614 and a return lumen 616 that are adjacent andlaterally offset from one another, such as the probe of FIG. 6G that hasan elliptical cross-section and defines circular delivery and returnlumens. Although FIGS. 6A-6G distinctly identify each lumen as adelivery lumen 614 or a return lumen 616, it should be understood thateach of the delivery and return lumens may be any particular lumen.Furthermore, other variations of the probe include other suitablecombinations of features with respect to shape, size, and number oflumens.

Variations in which the probe has coaxial or otherwise adjacent deliveryand return lumens may have a more uniform probe temperature. Forexample, as shown in FIGS. 5A and 5B, the probe 510 may maintain asubstantially uniform probe temperature because the probe 510 thermallyexposes the coldest coolant 570 entering the treatment segment of theprobe in the delivery lumen 514 to the warmest coolant 570 exiting thetreatment segment of the probe in the return lumen 516. In othervariations, the probe may include insulation between the delivery andreturn lumens to reduce a warming effect of the warmer coolant in thereturn lumen on the cooler coolant in the delivery lumen.

As shown in FIGS. 7A-7C, in some variations, the probe 710 may include atemperature sensor 718 to monitor temperature of the outer surface 712of the probe 710 (i.e., the adipose tissue interface surface) and/ortemperature of the coolant 770. The temperature sensor may be, forexample, a thermocouple or a thermistor, and may communicate throughsensor wire 719 to the control subsystem (not shown) which may modulateone or more parameters (e.g., flow rate, cooling rate in the coolingsubsystem) of the system in order to achieve a particular temperature(e.g., to maintain a particular target temperature of probe and/orcoolant, or to modulate the temperature of the probe and/or coolant).The sensor wire 719 may travel along the probe 710 to the sensor 718 ina lumen that is separate from the delivery lumen 714 and return lumen716. For example, as shown in FIG. 7B, the sensor wire 719 may travelalong a lateral lumen adjacent to the delivery lumen 714, oralternatively the lateral lumen may be adjacent to the return lumen 716.As another example, as shown in FIG. 7C, the sensor wire 719 may travelalong a central lumen. However, in other variations, the sensor wire 719may travel along the delivery lumen and/or return lumen, and may beprotected from the coolant with insulation or in another suitablemanner. In other variations, the temperature sensor may include anysuitable kind of sensor and/or may communicate with the controlsubsystem wirelessly.

Although FIG. 7A depicts a single temperature sensor located on thedistal end of the probe 710, in other variations of the probe, thetemperature sensor may be located at any suitable point along thetreatment segment or other suitable portion of the probe. Furthermore,in other variations, the probe 710 may include multiple temperaturesensors. For example, the probe 710 may include multiple temperaturesensors arranged at different respective axial and/or circumferentiallocations on the probe. At least some of the wires of multipletemperature sensors may travel independently along the probe (e.g.,longitudinally at different circumferential locations) or may be bundledto travel together along the probe.

The probe may be structured to accommodate different kinds of coolant inthe probe, including gaseous, liquid, and/or semi-solid or solid formsof coolant. In some variations, the probe may cool the surroundingadipose tissue by permitting the coolant to undergo phase changes as aresult of absorbing heat from the tissue. For example, as shown in FIGS.8A and 8B, the probe 810 may carry a liquid coolant 870L in an outer,annular delivery lumen 814 toward the treatment segment at the distalend of the probe that underlies skin 50.

FIG. 8B is a cross-sectional view taken along line B-B of FIG. 8A. Whenpassing through the treatment segment of the probe, coolant 870L absorbsheat from and cools the surrounding tissue, which may cause the coolantto vaporize. The wall 815 separating the delivery lumen 814 and thecentral return lumen 816 may be porous, such that the vaporized, gaseouscoolant 870G passes through the porous wall 815 from the outer annulardelivery lumen 814 into the central return lumen 816. Any suitableportion of the wall may be porous to allow transfer of coolant. Theprobe 810 then may carry the gaseous coolant 870G in the central returnlumen 816 away from the treatment segment of the probe toward a proximalportion of the probe. In the proximal portion of the probe or a separatecomponent in fluidic communication with the probe, a cooling subsystem(such as cold reservoir 830, as described further herein) may chill thecoolant such that the coolant 870G releases heat 833 and condenses backinto liquid coolant 870L. After cooling and condensing into a liquidphase, liquid coolant 870L may continue to circulate again throughdelivery lumen 814. This cycle of coolant vaporization and condensationmay be repeated over time in order to reduce the temperature of the skin50.

As another example, as shown in FIG. 8C, the probe 810 may usevaporization of pressurized coolant to induce a phase change in thetreatment segment of the probe that absorbs heat from and consequentlycools the surrounding tissue. As shown there, the probe 810 carries aliquid coolant 870L in a central delivery lumen 814 toward the treatmentsegment of the probe configured for insertion into adipose tissueunderlying the skin. When passing through the treatment segment of theprobe, coolant 870L absorbs heat from and cools the surrounding tissue,which may cause the coolant to vaporize. Similar to the example depictedin FIG. 8B, the wall 815 separating the delivery lumen 814 and thereturn lumen 816 may be porous such that the vaporized, gaseous coolant870G passes through the porous wall 815 from the central delivery lumen814 to the outer, annular return lumen 816.

Although FIG. 8C depicts only a distal portion of the wall 815 betweenthe delivery and return lumens as being porous, all or any othersuitable portion of the wall 815 may be porous to allow transfer ofgaseous coolant 870G into the return lumen 816. The probe 810 may thencarry the gaseous coolant 870G in the return lumen 816 away from thetreatment segment of the probe. In some variations, the gaseous coolant870G may be cooled and condensed by a cooling subsystem similar to thatdescribed above with reference to FIG. 8A. In another variation, asshown in FIG. 8C, the gaseous coolant 870G may be exhausted out of theprobe 810. In this variation, the probe may comprise a valve 852 thatmodulates the exhaust of the gaseous coolant 870G. By controlling therate of exhaust, the valve may control the pressure inside the probe andthe rate at which the liquid coolant vaporizes, and therefore the valvemay indirectly control the rate of heat transfer from the tissue to thecoolant and the degree of cooling of the probe and surrounding tissue.The valve coupled to the return lumen 816 may control the rate of aphase transformation of the coolant 870G across the porous wall 815.Other aspects of flow control depicted in FIG. 8C including the liquidreservoir 870L and nozzle 854 are described in further detail later withrespect to the coolant cooling subsystem.

In some variations of probes carrying liquid coolant, as shown in FIG.8B, the liquid coolant 870L may be directed in the delivery lumen 814through capillary action along a passive fluid distributor such as wick880. The wick 880 may include, for example, porous sintered copperbeads, but may additionally or alternatively include any suitablematerial for conducting liquid coolant 870L in the delivery lumen 814.In other variations, the probe 810 may include other mechanisms forinducing directional flow of liquid coolant 870L and/or gaseous coolant870G, such as pressure differentials or temperature gradients.Furthermore, different variations of the probe 810, with differentshapes, sizes, and/or relative orientations of the delivery lumen 814and the return lumen 816 may similarly implement this principle ofcoolant vaporization and condensation to cool adipose tissue.

In other variations, the one or more delivery lumens and one or morereturn lumens may be integrated into a single lumen. For example, asshown in FIG. 6H, a single lumen probe may carry coolant both toward andaway from the distal end of the treatment segment, by being coupled tomultiple fluid distributors that collaborate to provide oscillating flowthrough the lumen. Such oscillating flow may similarly be implemented inlumens of multi-lumen probes. As another example, as shown in FIG. 9, asingle lumen probe 910 may contain a solid or semi-solid coolant 970 inat least the treatment segment of the probe 910.

In some variations, as shown in FIG. 9, the probe 910 may carry a frozencoolant 970 (e.g., frozen gel or liquid) in at least the treatmentsegment of the probe 910. The frozen coolant 970 may have a melt orsublimation temperature such that the frozen coolant 970 undergoes phasechange at a certain temperature (e.g., from solid to liquid or fromsolid to gas). This phase change may take advantage of latent heat offusion in order to absorb energy and keep the probe 910 at a constant,cold temperature. In some variations, the frozen coolant 970 may be aninsert that, when melted or sublimated, may be exchanged for anotherfrozen coolant insert.

In some variations, as shown in FIGS. 22A and 22B, single lumen probes2200, 2250 may be inserted into a patient body 2240, 2290 respectively.In FIG. 22A, a distal portion of the probe 2200 is inserted into thebody 2240. A proximal portion of the probe 2200 is open-ended and may beclosed by a detachable sealing member 2230 such as a cap. The coolantmay be solid or semi-solid, and may be exchanged with new coolant or theprobe may be replaced entirely with a new probe. In some variations, theprobe is inserted between the surface of the skin and a target bloodvessel such as a vein (not shown). In this manner, the probe may coolthe adipose tissue between the skin and a blood vessel. In one example,the coolant may be ice or saline ice.

FIG. 22B shows an open-ended probe 2250, with an enclosed distal portionand an open-ended proximal portion. A distal portion of the probe 2250is inserted into the patient body 2290. Coolant injector 2280 may injecta pressurized liquid coolant 2270 a into a lumen of the probe 2250. Asheat is absorbed from the body 2290 by the probe 2250, the liquidcoolant 2270 a will begin to undergo a phase change by boiling andcondensing. The resulting vapor coolant 2270 b will expand and willnaturally be vented out of the open-ended proximal portion of the probe2250, thereby reducing the temperature of the target adipose tissue.

The coolant injector 2280 may be removed from the probe 2250 afterinjecting coolant 2270 a or may remain within the probe 2250, so long asthe coolant vapor 2270 b is able to vent out from the open-ended portionof the probe 2250. Additionally or alternatively, the coolant injector2280 may continuously sputter liquid coolant 2270 a into the tube or beinserted and removed from the probe 2250 periodically in a predeterminedcycle to replace and replenish the coolant 2270 a as needed. The coolantinjector 2280 is not limited in shape so long as vapor coolant 2270 bmay vent from a proximal portion of the probe 2250. The probe 2250 mayadditionally or alternatively include a plurality of lumens such asthose illustrated in FIGS. 6A-6G where liquid coolant 2270 a isdelivered through a delivery lumen and vapor coolant 2270 b is ventedout of the probe 2250 via a return lumen.

One more temperature sensors may also be provided to the probe 2200,2250 to determine when the probe is no longer providing a desiredcooling effect (e.g., when coolant has melted). A solid coolant 2220 mayhave a melt or sublimation temperature such that the coolant 2220undergoes phase change at a certain temperature. The cooling members2200 and 2250 may be formed of a biocompatible metal suitable fortransferring heat such as those described elsewhere, including but notlimited to stainless steel or a polymeric material, for example.Additionally, or alternatively, the cooling members illustrated in FIGS.22A and 22B may be placed externally on a surface of the skin.

In some variations, the outer diameter of the treatment segment of theprobe may be between approximately 3 millimeters and approximately 10millimeters, or may be between 5 millimeters and 8 millimeters. In somevariations, the length of the treatment segment of the probe may be atleast approximately 10 millimeters to approximately 300 millimeters, ormay be more than 300 millimeters. For example, the treatment segment ofthe probe may be approximately 6-7 millimeters in diameter and 100millimeters long. However, the overall dimensions of the probe may varybased on the characteristics of the area in which the probe will beinserted, as well as various aspects of the probe and coolant. Forexample, some factors affecting the desired size of the probe includethe thickness of the adipose tissue (correlating to depth of the targetblood vessel under the skin), length and diameter of the treatmentportion of the target blood vessel, and thermal characteristics of thematerial of the probe (e.g., thermal conductivity, wall thickness) andcoolant (e.g., specific heat capacity, flow rate). Accordingly, theabove-listed dimensions are only exemplary, and may vary depending onthe specific application of the device and system.

In some variations, at least the adipose tissue interface surface of theprobe may include a biocompatible metal suitable for transferring heatfrom surrounding tissue to the coolant within the probe, and thereforeeffectively cooling the surrounding tissue. For example, the probe mayinclude stainless steel (e.g., grade 316L), stainless steel clad copper,or stainless steel clad aluminum. In other variations, the probe mayinclude a polymeric material. Generally speaking, the probe may be arigid or a semi-rigid material, but in other variations, the probe maybe flexible. However, the probe may generally include any suitablecombination of materials. In some variations in which the probe isflexible, the probe may additionally include a stylet and/or a guidewireto help navigate the probe to the treatment area.

Although the system is generally shown in the figures as having oneprobe, in other variations, the system may include two or more probes.In some variations, multiple probes may be placed in series in thetissue overlying the target blood vessel, such as to track the curvatureof blood vessel. Additionally or alternatively, each probe may be placedin the tissue overlying a respective target blood vessel, such as toperform cryolipolysis above multiple blood vessels simultaneously.

Guide Member

In one variation, the system may include a guide member to help positiontreatment segments of the fluidic channel appropriately over the targetblood vessel. In some variations, as shown in FIGS. 15A and 15B, thesystem may comprise a guide member 1568 configured to help guide thepositioning and/or orientation of the probe 1510 of the device 1502 inthe adipose tissue of the patient. For instance, the guide member 1568may be used to position the probe at a particular depth in the adiposetissue 52 to target a selected portion of tissue, to help prevent theprobe 1510 from damaging the target vessel 60 and other tissue whoseprotection is desired, and/or any suitable purpose. The guide member mayadditionally or alternatively be used to help position the probe at aparticular rotational orientation (e.g., to position the insulator1564). In some variations, the guide member 1568 may include a magneticmaterial, such as a permanent magnet or a ferromagnet that repels and/orattracts one or more components of the cooling device 1502. The guidemember 1568 may, for example, include a magnetic material that repels orattracts at least a portion of the probe 1510 (or a component coupled tothe probe, such as insulator 1564).

As another example, the guide member 1568 may repel a first portion ofthe probe 1510 or component coupled to the probe 1510, and the guidemember 1568 may further attract a second portion of the probe 1510 orcomponent coupled to the probe. However, the guide member 1568 mayinteract with the probe 1510 in any suitable manner. The size and shapeof the guide member 1568 may vary depending on the specific application.For example, a magnetic guide member 1568 may induce a strongerrepelling or attracting magnetic force against the probe 1510 (e.g., byhaving a larger size or greater magnetic strength), in applications inwhich the controlling magnetic force traverses a greater amount oftissue between the guide member 1568 and the probe 1510 when insertedinto the patient. That is, when the layer of adipose tissue between theprobe and the exterior surface of the skin is greater.

For a guide member 1568 comprising one or more permanent magnets on theskin surface 50, ultrasound may be used to identify and mark thelocation of the target vessel on the skin surface 50. The permanentmagnets of guide member 1568 may be attached to the skin surface overthe target vessel by way of straps and/or adhesive, for example. Theguide member 1568 may all be magnetic or have one or more portions thatare magnetic. In one variation, an incision may then be made in thepatient for insertion of a cooling probe under the skin 50 and tunneled.The probe 1510, having a the tip which may be flexible, may be guided bythe permanent magnets of the guide member 1568 under the skin surface 50through an attractive force between the two such that the cooling probetunnels and resides in a desired location above the target vein segmentduring a treatment session. As a secondary effect, the attractivemagnetic force between the guide member 1568 magnet and the probe 1510may in some instances compress the interposed tissue to reduce bloodflow between the two structures, thereby facilitating greater cooling ofthe interposed tissue.

As shown in FIG. 15A, in one variation, the guide member 1568 may beexternal to the patient, such that the guide member 1568 may be movedalong the surface of the skin 50 (or another external surface) and guidethe position and/or orientation of the probe 1510 through the skin 50and any tissue located between the probe 1510 and the skin 50. As shownin FIG. 15B, in another variation, the guide member 1568 may be insertedinto the treatment portion of the target vessel 60 itself, under theprobe 1510 and used to locate the probe 1510 adjacent to the vessel 60.In this variation, the guide member 1568 may repel at least a portion ofthe probe 1510, such as to help prevent the probe 1510 from approachingtoo close and risk damaging the target vessel 60. In yet anothervariation, the guide member 1568 may be inserted in another portion ofthe adipose tissue or other internal patient tissue in order to interactwith and guide the probe 1510.

Alternatively, the guide member 1568 may repel the probe throughmagnetism from touching the vessel surface if it were desirable toprevent direct cooling of the vessel tissue. In yet another variation,the guide member 1568 in the vessel 60 may be used to rotationallyorient the probe 1510 relative to the vessel such that an insulativeportion of the probe 1510 is positioned to reside between the activecooling probe 1510 and the vessel 60 wall. Again, rotational alignmentforces may be induced via magnetism.

In some variations, the system may comprise a reference marker to helpposition the probe using imaging techniques. In some variations, asshown in FIG. 15C, the reference marker 1569 may be coupled to theprobe, or may be coupled to a component coupled to the probe. Forexample, the imaging marker 1569 may be a cylindrical radiopaque markercoupled circumferentially around the treatment segment of the probe1510. The radiopaque marker 1569 may be visible under fluoroscopy orother imaging modalities. The radiopaque marker may include, forexample, tantalum, and/or suitable radiopaque materials. Although theimaging marker depicted in FIG. 15C is ring-shaped, the imaging markermay be rectangular or any other suitable shape. Furthermore, in othervariations, the imaging marker may be an etching (e.g., a cross-mark) onthe probe 1510 or other component coupled to the probe 1510.

External Cooling Devices

Also described herein are external cooling devices and systems. As shownin FIG. 17, in some variations, an external cooling device forfacilitating percutaneous access to a target blood vessel in a patientmay comprise a cooling member 1710 with an elongate fluidic channel 1712to carry a coolant, and a securing member 1760 to couple the coolingmember 1710 to an external surface of the patient (not shown). In somevariations, as described further below, the coolant may be a fluid suchas a liquid or gas, but in other variations, the coolant may be a solidor a semi-solid, such as a gel. The fluidic channel may include one ormore treatment segments (e.g., 1712 a or 1712 b) to cool a selectedportion of adipose tissue, and the securing member 1760 may beconfigured to couple at least a portion of the cooling member 1710 tothe patient such that the treatment segment of the fluidic channeloverlies and is substantially aligned with a treatment portion of thetarget blood vessel. In such a configuration, the treatment segment ofthe fluidic channel may provide an external cooling source to cool and,over time, reduce the volume of tissue overlying the treatment portionof the target blood vessel. In some variations, the external coolingdevice may be part of a system 1700 that further includes a coolingsubsystem 1720 with a cooling mechanism 1730 that modifies thetemperature of the coolant and a pump that receives coolant from thecooling mechanism and delivers coolant to the probe. In some variations,the system may further include a control subsystem 1750 that controlsthe flow rate and/or temperature of the coolant.

Cooling Member

As shown in FIG. 17, the cooling member 1710 may include a fluidicchannel 1712 such as tubing configured to carry a coolant 1722. Thecooling member 1710 may include one, two, three, or more than threetreatment segments, where each treatment segment is configured toprovide an external cooling source to cool adipose tissue overlying arespective treatment portion of a target blood vessel. Some treatmentsegments may be configured to provide supplementary cooling sources tocool adipose tissue overlying the same portion of a target vessel. Insome variations, such as that as shown in FIG. 17, the cooling member1710 may be configured to target adipose tissue overlying the basilicvein and the cephalic vein in the upper arm of the patient. In thisvariation, the fluidic channel 1712 may include a first treatmentsegment 1712 a and a second treatment segment 1712 b. The firsttreatment segment 1712 a may be configured to track a treatment portionof the cephalic vein, and the second treatment segment 1712 b may beconfigured to track a treatment portion of the basilic vein.Accordingly, the relative orientations of the first and second treatmentsegments of the fluidic channel may be similar to that of the cephalicand basilic veins. However, in other variations, the size, shape, andnumber of treatment segments of the fluidic channel 1712 may varydepending on the application. For example, the first and secondtreatment segments 1712 a and 1712 b may be parallel. As anotherexample, the fluidic channel 1712 may include only one treatmentsegment.

In some variations, the cooling member 1710 may include a temperaturesensor 1718 (e.g., thermocouple or thermistor) that measures thetemperature of the coolant 1722 and/or cooling member 1710 at any pointalong the cooling member 1710. For example, as shown in FIG. 17, thetemperature sensor may be located on an internal or external surface ofa treatment segment (e.g., 1712 a or 1712 b) or on an internal orexternal surface of another portion of the fluidic channel 1712. In somevariations, the cooling member 1710 may include multiple temperaturesensors arranged at multiple locations along the cooling member 1710.Similar to the system including an internal cooling device describedabove, the measured one or more temperatures of the coolant 1722 and/orcooling member 1710 may be provided to the control subsystem 1750.

The fluidic channel 1712 may have any suitable diameter. For example,the fluidic channel 1712 may have an inner diameter between about ⅛ inchand about ½ inch, or between about ¼ inch and about ⅜ inch. In somevariations, the fluidic channel 1712 may comprise a flexible material,such as polypropylene, nylon and/or other suitable flexible materials(e.g., PVC, Tygon, silicone, deformable copper or stainless steeltubing, or the like). When the fluidic channel 1712 comprises a flexiblematerial, it may be configured to conform to the patient's tissue,and/or may be configured to be shaped to trace the target vessels (e.g.,the basilic and/or cephalic veins). However, it should be appreciatedthat in some variations, the tubing may be made from a rigid orsemi-rigid material.

In yet other variations, the internal configuration of the probesdisclosed in FIGS. 5-9 and 22 such as the size, shape and number oflumens may be provided as the internal configuration of the externalcooling member as well.

Securing Member

A securing member may be configured to directly or indirectly couple acooling member to an external surface of the patient such that atreatment segment of the fluidic channel overlies and is substantiallyaligned with a treatment portion of the target blood vessel. In otherwords, the securing member may secure the treatment segment of thecooling member against the skin overlying the treatment portion of thetarget vessel. In other variations, the securing member may be omitted.For example, the cooling member may independently couple to the patient,such as by self-adhering to the skin of the patient.

As shown in FIGS. 17 and 18, in some variations, the securing member maycomprise a cuff that is configured to couple to the patient with aradially compressive force. For example, as shown in FIG. 17, cuff 1770may couple to the cooling member 1710 and wrap around a limb (e.g.,upper arm) of the patient. The cuff 1770 may include a tissue interfaceside 1762 that is configured to contact an external surface (e.g., skin)of the patient, and a second side opposite the tissue interface side1762. In this variation, the cuff 1770 may wrap around a limb of thepatient and secure the cooling member 1710 in place by joining the firstend 1766 with the second end 1768 of the cuff 1770. The first and secondends 1766 and 1768 may couple to one another with hook and loopfastener, ties, hooks and eyes, belt loops, zippers, snaps, and/or anysuitable fasteners. Additionally or alternatively, the cuff 1770 mayinclude a tubular sleeve that slips over the limb of the patient andsecures to the patient with elastic, cinching ties, and/or any suitablefastener. As shown in FIGS. 18A-18C, the first end 1866 and the secondend 1868 of the cuff 1870 may join in a manner similar to the joiningmechanisms of the first end 1766 and second end 1768 of cuff 1770depicted in FIG. 17.

As shown in FIG. 19, in some variations, the securing member 1902 mayinclude at least one adhesive dressing which may be applied to thecooling member 1910. For example, in the variation depicted in FIG. 19,the securing member may include one or more adhesive strips 1970 thatare configured to adhere to an external surface of the patient and holdthe one or more treatment segments 1912 against the patient. The stripsmay be applied cross-wise relative to the treatment segments orlongitudinally along the treatment segments, or in any suitableorientation. In some variations, the one or more adhesive dressings maybe large and cover all or a substantial portion of the entire treatmentsegment 1912 and/or other portions of the cooling member 1910. In somevariations, the one or more adhesive dressings may be pre-attached tothe cooling member 1910 such that the relative positions of any multipletreatment segments 1912 may be established prior to their placement onthe patient. In other variations, the one or more adhesive dressings maybe attached to the cooling member 1910 after placing the one or moretreatment segments 1912 on the patient, such that the relative positionsof any multiple treatment segments 1912 may be adjusted before beingsecured to the patient by the adhesive dressings 1970.

In some variations, the securing member may be circumferentiallyadjustable, to accommodate patient limbs of a variety of sizes and/or toenable variable compressive force of the cooling member against theskin. Increasing the compressive force of the treatment segments of thefluidic channel may force the treatment segments deeper into the tissueof the patient, thereby increasing the depth at which tissue coolingoccurs. In one variation, as shown in FIG. 18A, the securing member mayinclude an inflatable cuff 1870 that wraps around a limb (e.g., upperarm) of the patient. The inflatable cuff may include one or moreinflatable cells adjustable in volume ranging from a deflatedconfiguration, a partially inflated configuration, and a fully inflatedconfiguration. Inflation may be controlled, for example, by one or morehand pumps 1874, but may additionally or alternatively be controlled byan automated pump. In versions of cuffs with multiple cells, each cellmay have its own respective inflation pump. The cells may be shaped witha flexible inner wall such that generally speaking, a higher degree ofinflation in the cuff will result in a smaller internal circumference ofthe cuff that presses the cooling member more forcefully against thetissue of the patient. The one or more cells may be fluidicallyconnected such that all cells are inflated in tandem.

Alternatively, each of the cells may be independent structure such thatsome of the cells may be at least partially inflated while other cellsmay be completely deflated. Such separate, independent adjustability mayenable different degrees of compression (and different depth ranges ofcooling) for different portions of the fluidic channel. For example, onecell may be coupled to or overlie a first treatment segment of thefluidic channel that corresponds to a first target vessel, while asecond cell may be coupled to or overlie a second treatment segment ofthe fluidic channel that corresponds to a second target vessel. In thisexample, if the two cells are inflated to different degrees, theresulting differential compressive forces on the first and secondtreatment segments against the skin of the patient may enable differentdepths of cooling. Such selective different depths of cooling may bedesirable, for example, if the two target vessels are located atdifferent tissue depths. In various versions, the inflatable cuff mayinclude a multi-dimensional array of inflatable cells (e.g., arectangular grid) acting like “pixels” of inflation pattern resolutionto permit a range of selective circumferential adjustability over thesurface area of the cuff.

In another variation of an adjustable securing member, as shown in FIG.18B, an adjustable cuff 1870 may secure the cooling member in place byjoining the first end 1866 with the second end 1868, overlapping thefirst and second ends to varying degrees. For instance, in somepositions, the first and second ends may fully overlap, which results ina decreased circumference of cuff 1870 and increased compressive force.In other positions, the first and second ends may only partiallyoverlap, resulting in an increased circumference of cuff 1870 anddecreased compressive force. The first and second ends 1866 and 1868 maycouple to one another with hook and loop fastener, ties, hooks and eyes,belt loops, zippers, snaps, and/or any suitable fasteners.

In some variations, the securing member may fix the position of one ormore segments of the fluidic channel. In one variation, as shown in FIG.17, at least a portion of the fluidic channel may be threaded throughthe securing member. For example, in the variation depicted in FIG. 17,the first treatment segment 1712 a and the second treatment segment 1712b of the fluidic channel may each thread through a respective series ofopenings 1764 on the securing member 1760 between a tissue interfacesurface 1762 of the securing member and the surface opposite the tissueinterface surface (not shown). This arrangement may fix the relativepositions of the one or more treatment segments 1712 a and 1712 b on thesecuring member 1770. Furthermore, this arrangement may isolate the oneor more treatment segments 1712 a and 1712 b on the tissue interfacesurface 1762, which may enable the one or more treatment segments todirectly contact and focus their cooling effect to only the skin of thepatient overlying a target vessel. However, in some variations, thesecuring member 1770 may permit some repositionability of the fluidicchannel 1712 by providing an array of openings 1763 through which thefluidic channel segments may be selectively threaded, such that one ormore of the fluidic channel segments is repositionable.

In other variations, the securing member may enable repositioning of oneor more segments of the fluidic channel on the securing member. Forexample, as shown in FIGS. 18A-18C, the securing member may include anattachment region 1872 to which the treatment segments 1812 a and 1812 bshown in FIG. 18D may be removably connected in various orientations.Although the securing member 1870 of FIGS. 18A-18C includes a singlerectangular attachment region 1872, it should be appreciated that thesecuring member 1870 may include any suitable number of attachmentregions in any suitable pattern and shapes.

In some variations, the attachment region 1872 may be larger than thetreatment segments 1812, such that the treatment segments 1812 may bepositioned in more than one location on the attachment region 1872,and/or in more than one relative orientation. For example, the firsttreatment segment 1812 a and the second treatment segment 1812 b in FIG.18D from respective branches 1873 may be positioned closer or fartheraway from one another, and/or at greater or smaller angles relative toone another, on an attachment region. Branches 1873 may meet at fluidicchannel 1810. The distance and/or orientation of the treatment segmentson the attachment region may depend on the specific application (e.g.,the anatomy of the patient). In variations in which the securing memberenables repositioning of one or more segments of the fluidic channel onthe securing member, the fluidic channel segments may couple to thesecuring member with hook and loop fastener (e.g., hook or loop may bewrapped fully or partially circumferentially around the fluidic channelsegments), adhesive tape, low-strength epoxy, and/or any suitablereversible manner.

In some variations, the securing member may include a temperaturesensor, such as to measure the temperature of the skin on or near thetreatment region overlying the target blood vessel. The temperaturesensor may include a thermocouple, a thermistor, or any suitable sensor.In one example, a temperature sensor may be located on a tissueinterface surface (e.g., surface 1762 as shown in FIG. 17) such thatwhen the securing member is coupled to the patient, the temperaturesensor is adjacent to the skin of the patient. In some variations, thesecuring member 1770 may include multiple temperature sensors arrangedat multiple locations on the securing member. For example, a temperaturesensor may be provided additionally or alternatively in the securingmember at a location to measure the temperature of the cooling member.Similar to the system including an internal cooling device describedabove, the measured one or more temperatures may be provided to thecontrol subsystem.

Coolant and Cooling Subsystem

As described above, coolants of various kinds may be used to cool theinternal probe and/or the external cooling member and the surroundingtissue. A discussion of variations of the coolant and cooling subsystemfor an internal probe is presented first and followed by variations ofthe coolant and cooling subsystem for an external cooling member.

In variations in which coolant is circulated through the probe, thecooling subsystem may include a cooling mechanism and a fluiddistributor. The cooling mechanism may modify the temperature of thecoolant, and the fluid distributor may deliver the coolant from thecooling mechanism to the probe. The cooling subsystem may be located ina separate unit in fluidic communication with the probe with tubing orother fluidic channels (e.g., cooling subsystem 220 depicted in FIG. 2in communication with probe 210), and/or integrated with a proximalportion of the probe (e.g., as shown in FIGS. 8A-8C). Furthermore,various features of the cooling subsystem, such as cooling fins or otherheat sinks, may additionally or alternatively be arranged anywhere alongthe fluidic pathway of the coolant to chill the coolant.

In some variations, as shown in FIGS. 10A and 10B, the cooling mechanism1030 may include a cooling tank 1036 and the fluid distributor 1040 mayinclude a pump. In a first example shown in FIG. 10A, in an open fluidicsystem, the cooling tank 1036 may include a reservoir of coolant (e.g.,a liquid coolant) that is in fluid communication with the probe 1010. Inthis example, the cooling tank 1036 may include a filter 1034 to purifyand/or reduce particulates and other matter from the coolant 1070 beforethe coolant 1070 is pumped into the probe 1010. The cooling tank 1036may include a heat pump, ice, and/or other suitable setup for coolingthe coolant 1070 or other fluid in the reservoir 1036. The reservoir maybe insulated with expanded polystyrene foam, a double-walled structure,and/or other suitable insulation materials. As depicted in FIG. 10A, thepump 1040 may be configured to actuate the coolant 1070 from the coolingtank 1036 from a downstream location relative to the cooling tank 1036.The fluid distributor 1040 may be, for example, a centrifugal pump, apositive displacement pump, a peristaltic pump, or any other suitablepump. In this example, the fluid distributor 1040 may actuate coolant1070 from the cooling tank 1036 and deliver the coolant 1070 to theprobe 1010. After circulating in the probe 1010, the coolant may returnfrom the probe 1010 and flow into the cooling tank 1036, which chillsthe coolant 1070 to be recirculated in the probe 1010 by fluiddistributor 1040.

In a second example, as shown in FIG. 10B, in a closed fluidic system,the cooling tank 1036 may include a heat exchanger 1032 that transfersto the surrounding medium 1071 (e.g., a second coolant) the heat fromthe coolant 1070 circulating within the heat exchanger 1032, therebycooling the coolant 1070. The cooling tank 1036 may be similar to thetank described above in reference to FIG. 10A, or any suitablevariation. As depicted in FIG. 10B, the fluid distributor 1040 may beconfigured to actuate the coolant 1070 through the cooling tank 1036from an upstream location relative to the cooling mechanism 1036. Inthis example, the fluid distributor 1040 may actuate coolant 1070 fromthe probe 1010 to pass through the heat exchanger 1032 and deliver thechilled coolant 1070 to the delivery lumen of the probe 1010. Aftercirculating in the probe 1010, the coolant 1070 may flow from the probe1010 into the fluid distributor 1040, which then actuates the coolant1070 toward the heat exchanger 1032 to be chilled and to recirculate inthe probe 1010.

In other variations, the cooling subsystem 1030 may be integrated into aproximal portion of the probe. For example, as shown in FIG. 8A, aportion of the probe 810 that is proximal to the distal treatmentsegment of the probe may be coupled to one or more heat sinks.

In particular, the proximal portion of the probe 810 may include a coldreservoir 830 (e.g., a scaled-down version of the cooling tank of FIG.10B) and/or cooling fins 832. The cold reservoir, cooling fins, and/orother heat sinks may absorb heat from the coolant flowing in or fromreturn lumen 816, thereby chilling the coolant 870 prior torecirculation in the probe 810.

In yet other variations, the coolant may originate from a reservoir thatcan be exchanged as the coolant needs replacement due to exhaustion oreventual warming of the reservoir. For example, as shown in FIG. 8C, areservoir of chilled coolant 870L may be attached directly to thedelivery lumen 814 of the probe 810. The variation depicted in FIG. 8Cincludes a fluid-tight, threaded connection 853 between the reservoir ofchilled coolant 870L and a proximal portion of the probe 810, and anozzle 854 that may help control flow of the coolant 870L into theprobe, but other variations may additionally or alternatively includeany suitable kind of connection, such as one with gaskets and/or valves.

In other variations, coolant may not circulate through the probe. Insome of these variations, the probe may be replaced during the procedurein order to maintain the desired temperature. For example, as describedabove with respect to FIG. 9, in variations in which a probe 910 carriesa frozen coolant insert 970, the frozen coolant insert 970 may beexchanged for another probe when the coolant insert 970 melts.Similarly, in the variation shown in FIG. 22A, the probe 2200 may bereplaced with a new probe.

Next, for variations of a cooling device comprising an external coolingmember, coolants of various kinds may be used in the treatment segmentof the cooling member to cool tissue. As shown in FIG. 17, in somevariations, the coolant 1722 may include a fluid that circulatesthroughout the cooling member 1710 and is chilled by cooling subsystem1720. The fluidic channel 1710 may include a delivery channel 1714 andreturn channel 1716. Delivery channel 1714 delivers chilled coolant 1722from outlet 1734 of cooling subsystem 1720 to the one or more treatmentsegments (e.g., 1712 a and 1712 b). Return channel 1716 receives thecoolant 1722 from the one or more treatment segments and returns thecoolant to the inlet port 1736 of cooling subsystem 1720. Coolingsubsystem 1720 may chills the coolant 1722 in preparation forrecirculation into the treatment segments.

Although FIG. 17 depicts a single delivery channel 1714 that divergesinto multiple treatment segments and a single return channel 1716 thatis formed by the merging of multiple treatment segments, in othervariations each treatment segment may be in fluidic communication with arespective delivery channel 1714 and/or respective return channel 1716.Accordingly, cooling subsystem 1720 may include multiple outlet ports1734 and/or multiple inlet ports 1736. In some variations, the deliverychannel 1714 and/or the return channel 1716 may be integrally formedwith the treatment segments 1712, while in other variations the deliveryand/or return channels are separate components that are fluidicallycoupled to the treatment segments.

In some variations, the cooling subsystem 1720 may include coolingmechanism 1730, similar to that described above with respect to systemsincluding an internal cooling device (e.g., the cooling subsystemsdescribed with reference to FIGS. 8-10). For example, the coolingmechanism 1730 may be similar to cooling mechanism 1030 shown in FIG.10A having an open fluidic system, in which the cooling tank 1036includes a reservoir of coolant (e.g., a liquid coolant) that is influid communication with the cooling member 1010.

As another example, the cooling mechanism 1730 may be similar to coolingmechanism 1030 shown in FIG. 10B having a closed fluidic system, inwhich the cooling tank 1036 includes a heat exchanger 1032 thattransfers to the surrounding medium 1071 (e.g., a second coolant fluid)the heat from the coolant 1070 circulating within the heat exchanger1032, thereby cooling the coolant 1070. However, any other suitablecooling subsystems may additionally or alternatively be included in thesystem.

For both a subcutaneous probe and cooling member, the coolant may be aliquid, vapor, or semi-solid or solid. Furthermore, as shown in FIGS. 8,9, and 22A-22B, the coolant may undergo a phase change while cooling theprobe and surrounding tissue, such that the coolant may take differentforms at different locations in the probe, cooling member and coolingsubsystem. Some exemplary coolant substances include saline,polyethylene glycol, and isopropyl alcohol. However, any suitablerefrigerant or other coolant may be used.

Generally, the coolant used in the subcutaneous probe and the coolingmember may have a temperature between about −10° F. and about 50° F. Insome variations, the coolant may have a temperature between about 0° F.and about 40° F. In other variations, the coolant may have a temperaturebetween about 10° F. and about 30° F. In other variations, the coolantmay have a temperature between about 20° F. and about 25° F. In yetother variations, the coolant may have a temperature of about 23° F.

In other variations, the probe and/or cooling member may be cooled inother ways aside from continuously chilling and recirculating chilledcoolant. In one variation, the cooling subsystem may simply chill thecoolant to a sufficient level prior to use of the probe and/or coolingmember on the patient, such that the coolant maintains its therapeuticcool temperature for a period sufficient to provide adequate cooling tothe adipose tissue.

In another variation, the probe and/or cooling member may include aself-cooling material whose cooling may be “activated” prior to use onthe patient. For example, the probe and/or cooling member may include afirst compartment containing ammonium nitrate or calcium ammoniumnitrate, and a second compartment containing water. The cooling of theprobe and/or cooling member may be activated when the contents of thecompartments are mixed (e.g., by breaking a separation between thecompartments) to cause an endothermic reaction that cools the probeand/or cooling member. In other examples, the probe and/or coolingmember may include compartments containing other substances that resultin an endothermic reaction when combined.

Control Subsystem

In some variations, a control subsystem may be coupled to the coolingsubsystem and control the flow rate and/or temperature of the coolant. Adiscussion of variations of a control subsystem for an internal probe ispresented first and followed by control subsystem variations for anexternal cooling member.

As shown in the block diagram of FIG. 11, in some variations, thecontrol subsystem 1150 may be coupled to a fluid distributor 1140 (e.g.,a pump) and/or a cooling mechanism 1130 (e.g., cooling reservoir ortank) of the cooling subsystem. The fluid distributor 1140 and coolingmechanism 1130 may cooperate to deliver a chilled coolant to the coolingmember 1110 (e.g., probe). As the coolant circulates in the coolingmember 1110 via delivery channel 1120 and return channel 1122, thecooling member 1110 and coolant absorb heat 1160 from and cools thetargeted adipose tissue in the patient 1100. The coolant then returnsfrom the cooling member 1110 to the cooling subsystem 1150 to be chilledand recirculated to the cooling member 1110.

Meanwhile, one or more temperature sensors in the cooling member 1110may provide the cooling member temperature 1152 (e.g., the temperatureof the adipose tissue interface surface) to the control subsystem 1150.Based on the measured temperature 1152 and a target temperature 1154input, the control subsystem 1150 may control the fluid distributor 1140to modulate the flow rate of the coolant and/or control the coolingmechanism 1130 to modulate the temperature or chilling rate of thecoolant in the cooling subsystem. For example, the control subsystem1150 may include a P, PI, or PID feedback controller to modulate thecoolant flow rate in order to reach a target temperature 1154 for theadipose tissue interface surface of the cooling member 1110.

In some variations, the control subsystem 1150 modulates one or moreparameters of the fluidic system to maintain turbulent flow of thecoolant, which may help promote cooling of the adipose tissuesurrounding the cooling member 1110. For example, the control subsystemmay modulate flow rate of the coolant (given a particular lumen size,coolant viscosity, and other selected fixed parameters) to maintain aReynolds number of at least approximately 4000. In some instancesselection of a coolant with low viscosity and avoidance of largepressure gradients across the fluidic system may additionally oralternatively help the control subsystem maintain turbulent flow. Inother variations, laminar flow of the coolant may be desirable.

Next, for variations of a cooling device comprising an external coolingmember, a control subsystem 1750 as shown in FIG. 17 may be coupled tothe cooling subsystem 1720 and may control the flow rate and/ortemperature of the coolant 1722 in external cooling member 1710. Thecontrol subsystem 1750 may be similar to the control subsystem 1150depicted in FIG. 11 and described in more detail above with respect tothe system including an internal cooling device. In particular, thecontrol subsystem 1750 may be coupled to a pump or other fluiddistributor and/or a cooling mechanism 1730. The pump and coolingmechanism may cooperate to circulate a chilled coolant to and from thecooling member 1710. Meanwhile, one or more temperature sensors in thecooling member 1710 and/or securing member 1770 may provide temperatureof the coolant, cooling member, and/or skin near the treatment region.Based on these measured temperatures and target temperature inputs, thecontrol subsystem 1750 may modulate the flow rate of the coolant and/orchill temperature or chill rate of the coolant in the cooling subsystem.For example, the control subsystem 1750 may include a P, PI, or PIDfeedback controller to maintain target temperatures. Like the controlsubsystem 1150 described above, the control subsystem 1750 may modulatevarious parameters to maintain turbulent flow of the coolant in thecooling member 1710, but may alternatively modulate various parametersto maintain laminar flow.

Peripheral Components

In some variations, the system may include other peripheral componentscoupled to one or more of an internal probe and/or external coolingmember that at least increase the effectiveness of cryolipolysis.

In some variations, the system may include other peripheral componentsdescribed in detail below. In one variation, the system may includeinsulation at one or more locations along the pathway of the coolant,such as to maintain the temperature of the coolant as much as possibleand to isolate the cooling effect to the selected portion of tissueoverlying the target blood vessel. For instance, the portions of fluidicchannel 1712 other than the treatment segments 1712 a or 1712 b may beinsulated similar to that described below with reference to FIG. 16B. Inanother variation, the system may include one or more vasoconstrictors(e.g., described below in reference to FIGS. 12A-12D) that decreaseperfusion of blood into the skin, thereby facilitating the cooling ofadipose tissue underlying the skin. In another variation, the system mayinclude mechanisms that hydrodissect and fracture adipose tissue (e.g.,mechanisms described with reference to FIG. 13B), thereby increasing thethermal conductivity of the adipose tissue and facilitating the coolingof the affected adipose tissue. In another variation, the system mayinclude an adipose tissue agitator that increases destruction of fatcell membranes (e.g., described with reference to FIG. 14, or avibrating mechanism coupled to the cooling member or securing member),thereby increasing the thermal conductivity of the adipose tissue andfacilitating the cooling of the affected adipose tissue.

Insulator

In some variations, the system may comprise insulation at one or morelocations along the pathway of the coolant, which may help to spatiallycontrol the areas that are cooled. In particular, in some variations, asshown in FIG. 15A, the probe 1510 may comprise an insulator 1564 thatextends axially along and at least partially circumferentially aroundthe probe 1510. The insulator may extend along at least an axial portionof the treatment segment, or any suitable axial portion, of the probe1510. Furthermore, the insulator 1564 may insulate only acircumferential portion of the probe 1510, such that the probe 1510 maycool tissue around only a portion of the circumference of the probe(e.g., a targeted region of adipose tissue of interest). For example, asshown in FIGS. 15A and 15B, the insulator 1564 may cover approximately180 degrees of a hollow circular cylindrical probe 1510. In othervariations, the insulator may cover a larger or smaller circumferentialportion of the probe 1510 (e.g., about 80 degrees to about 300 degrees,about 120 degrees to about 260 degrees, about 160 degrees to about 220degrees). As shown in FIG. 15A, in one variation, the probe 1510 of thecooling device 1502 may be inserted in adipose tissue directly below theskin 50, oriented such that at least a portion of the insulator 1564 islocated between the probe 1510 and the skin 50. This orientation maydirect the cooling away from the skin and/or help shield the skin fromcold.

As shown in FIG. 15B, in another variation, the probe 1510 of thecooling device 1502 may be inserted in adipose tissue directly above thetarget vessel 60, oriented such that at least a portion of the insulator1564 is located between the probe 1510 and the target vessel 60. Thisorientation may direct the cooling away from the target vessel 60 and/orhelp shield the target vessel 60 from cold. However, in othervariations, the probe 1510 with insulator 1564 may be placedapproximately halfway between the skin 50 and the target vessel 60, orat any suitable tissue depth and oriented with the insulator 1564shielding or protecting any suitable region of tissue. In somevariations, the insulator may include a material that is biostableand/or biocompatible, such as silicone rubber, or any other suitablematerial, that is coupled to the probe with an interference fit (e.g.,an insulating sleeve slipped over the probe), epoxy, threads, or anysuitable fastening means. In some variations, the insulator mayadditionally or alternatively be formed out of a thickened wall portionof the probe 1510.

In some variations, as shown in FIG. 16A, the probe 1610 mayadditionally or alternatively comprise an insulator 1664 thatcircumferentially surrounds at least a portion of the probe 1610 that isin contact with the skin 50 when the probe 1610 is inserted into thepatient (i.e., a transcutaneous segment of the probe 1610). In thisvariation, the transcutaneous segment of the probe 1610 is insulated tohelp protect skin 50 from cold. Like the insulators 1564 depicted inFIGS. 15A and 15B, the insulator 1664 may include a material that isbiostable and/or biocompatible and coupled to the probe in the mannerdescribed above, and/or include a thickened wall portion of the probe1610. Transmission lines 1656 (e.g., delivery channel, return channel)provide coolant to and/or from probe 1610.

In some variations, as shown in FIGS. 16A and 16B, the system mayadditionally or alternatively include an insulator 1666 in or aroundtransmission lines 1656 delivering coolant to and/or from the probe1610. The insulator 1666 may help maintain the temperature of thecoolant passing through the transmission lines 1656. For example, thetransmission lines 1666 passing between the cooling subsystem and theprobe may include polyvinyl chloride tubing and foam rubber insulation.However, in other variations, the transmission lines 1656 and insulator1666 may include any suitable material.

Vasoconstrictor

In some variations, the system may include a vasoconstrictor fordecreasing perfusion of blood into the skin 50. Perfusion of blood intothe skin may bring heat into the general treatment area of desiredcooling, which may hamper or inhibit the desired outcome of adipose celldeath. Vasoconstriction may decrease such perfusion and the amount ofheat in the skin, thereby reducing interference with effective coolingof underlying adipose tissue. The vasoconstrictor may be coupled to atleast one of the internal probe or external cooling members depending onthe type of vasoconstrictor utilized.

In some variations, as shown in FIG. 12A, the vasoconstrictor 1290 maybe applied externally to the skin in order to cool the skin to atemperature cold enough to induce vasoconstriction, but not cold enoughto cause cell death (e.g., between about 30° F. and about 35° F., orabout 32° F.). For example, the vasoconstrictor may be a cold object1292 placed adjacent to the skin 50, such as an ice pack or a highlythermally conductive metal like aluminum.

In some variations, positive or negative pressure is applied externallyto the skin to cause vasoconstriction. As shown in FIG. 12B, thevasoconstrictor 1290 may include a source 1296 of positive pressureapplied externally to the skin. For example, the vasoconstrictor 1290may be a weight, or a cuff that is worn around the skin and is radiallyadjustable with elastic, drawstrings, hook and loop fastener, inflation,or other adjustable mechanisms.

In some variations, as shown in FIG. 12C, the vasoconstrictor 1290 mayinclude a source of negative pressure. For example, a suction cup 1298,cuff or other sealable item may be applied to the treatment site andattached to a vacuum. Reduction of pressure within the suction cup 1298may compress vasculature in the skin at the boundary of the suction cup,thereby causing vasoconstriction of blood vessels supplying the skin 50in the treatment area.

In yet other variations, as shown in FIG. 12D, the vasoconstriction maybe caused by vasoconstrictive medication 1294, such as epinephrinecream, which is applied topically over the treatment site. Furthermore,the system may include any other suitable kinds of vasoconstrictors thatreduce perfusion of blood into the skin. As shown in FIGS. 12A-12D, thevasoconstrictor may be operated while the probe 1210 cools the adiposetissue 52 underlying the skin 50, but in other variations, thevasoconstrictor may additionally and/or alternatively be operated priorto the insertion of the probe. In other variations, the system mayinclude any suitable combination of vasoconstrictors.

Hydrodissector

In some variations, the system may include mechanisms that hydrodissectadipose tissue. Hydrodissection may be used to fracture the structure ofthe adipose tissue overlying the target vessel. Such fracturing mayincrease thermal conductivity of the adipose tissue such that thecooling probe has a greater therapeutic cooling reach, thereby allowingfor reduction of a greater volume of adipose tissue. Hydrodissection mayalso involve the introduction of saline or another suitable fluid intothe adipose tissue, where the fluid helps conduct cold within theadipose tissue.

In some variations, hydrodissection may be performed prior, or in closeproximity, to insertion of a cooling probe (e.g., the probes describedherein) and/or application of an external cooling member. In othervariations, the hydrodissection may additionally or alternatively beperformed simultaneously with the insertion of a cooling probe.Hydrodissection may be performed using a separate hydrodissection tool,or it may be performed using a cooling probe, such as the probesdescribed herein, configured for hydrodissection. Depending on thelength over the vessel that is hydrodissected, a volume of liquidbetween 1 cc and 20 cc may be used to hydrodissect adipose tissue with anear immediate effect.

In some variations, a target vessel is first located, such as viaultrasound, for insertion of a hydrodissection tool into adipose tissueabove the target vessel. Fluid may then be injected to fragment adiposetissue. Thereafter, cryolipolysis treatment may be applied as discussedabove.

In one example, as shown in FIG. 13A, the treatment segment of the probe1310 inserted into adipose tissue 52 overlying the target vein 60 mayinclude one or more fenestrations 1311 or pores that permit flow ofsaline or another suitable fluid from within the probe (e.g., a lumenfor saline flow), through the adipose tissue interface surface of theprobe, and into the surrounding adipose tissue 52. Thereafter, aninternal and/or external cooling member may be applied to performcryolipolysis as described above. In another example, as shown in FIG.13B, hydrodissection may involve the injection of saline or anothersuitable fluid through the skin 50 into the adipose tissue 52 with asecondary instrument such as a syringe 1320. Thereafter, an internaland/or external cooling member may be applied to perform cryolipolysisas described above. In other variations, the system may include anysuitable combination of mechanisms for hydrodissection.

Tissue Agitator

In some variations, the systems described herein may comprise a tissueagitator that agitates lipid crystals within fat cells in the adiposetissue, which may increase destruction of the fat cell membranes. Suchdestruction may enable the cooling probe to have a greater therapeuticeffect, thereby allowing for reduction of a greater volume of adiposetissue. In some variations, the agitation may be performed using acooling probe, such as the probes described herein. In other variations,the agitation may be performed by a separate tissue agitator. In somevariations, the tissue agitator may be external to the patient. In onevariation, a tissue agitator may be held to the surface of the skineither manually or using a strap and/or adhesive.

Similar to hydrodissection described above, tissue agitation may beperformed prior to and/or simultaneously with insertion of a coolingprobe into adipose tissue. In one variation, the lipids of the adiposetissue are crystalized before inducing vibration in the probe orapplication of an external tissue agitator on the surface of the skin.In some variations, agitation may be provide in a frequency range of 1Hz to 300 Hz. However, tissue agitation may be provided during coolingtreatment as well.

In one example, as shown in FIG. 14, the tissue agitator may include anexternal mechanical source of vibration such a vibrating motor 1462(e.g., a brushed DC motor with an eccentric mass coupled to its shaft)that is applied adjacent to skin 50 above probe 1410 to vibrateunderlying adipose tissue 52. In another example, the tissue agitatormay be configured to be located within adipose tissue, such as avibrator that is coupled to or incorporated into the probe, and/or aseparate vibrating source such as a second probe that vibrates. Inanother example, the tissue agitator may comprise an external and/orinternal source of acoustic vibration. In other variations, the systemmay comprise any suitable combination of tissue agitators.

Tissue Gatherer

In some variations, the system may include a tissue gatherer deviceconfigured to gather one or more portions of patient tissue toward thecooling device. This may have benefits such as allowing the coolingdevice to make better contact with the tissue, or better isolating thecooling to the adipose tissue to be treated by the cooling device. Inone variation, the system may gather patient tissue using negativepressure. FIGS. 20A and 20B show a cross-sectional view and aperspective view, respectively, of one variation of a cooling device2002 configured to pull a one or more portions of the patient's tissuetoward the cooling device 2002. The cooling device 2002 may include atissue cup 2090, a cooling member 2010, a securing member 2070, and avacuum source 2092. The tissue cup 2090 may have a concave shape todefine a volume for holding tissue, and the cooling member 2010 may belocated on an inner tissue interface surface of the tissue cup 2090. Thevolume defined by the tissue cup 2090 may be connected via a port 2094and tubing 2096 to the vacuum source 2092. The tissue cup 2090 may bemade of plastic or other suitable air-tight and/or insulating material.Securing member 2070 may be coupled to the tissue cup 2090 (e.g., withsutures or epoxy), and may be configured to secure the tissue cup 2090to the patient such that cooling device 2010 is adjacent to thetreatment area. When the vacuum source 2092 is activated, it may createa region of negative pressure within the tissue cup 2090, therebypulling the tissue of the patient toward the tissue cup 2090 and againstthe cooling member 2010.

In some variations, the cooling device 2002 may include a single tissuecup 2090 and a single cooling member 2010. However, in other variations,the cooling device 2002 may include any suitable number of tissue cupsand/or cooling members. For instance, the cooling device 2002 mayinclude two tissue cups, each with a respective cooling member, whereeach tissue cup and cooling member combination may be configured to coola region of tissue overlying a respective target blood vessel.

In another variation, the tissue gatherer may grasp the patient tissue.FIGS. 21A and 21B show a cross-sectional view and a perspective view,respectively, of another variation of a cooling device 2102 configuredto pull one or more portions of patient tissue toward the cooling device2102. In this variation, the cooling device 2102 may include a set ofjaws 2190 and a cooling member 2110. The jaws may be made of a rigidplastic, or any other suitable rigid or semi-rigid material. The jaws2190 may be movable between an open configuration and a closedconfiguration, such as by providing and releasing tension in pull wires2194 using a handle 2196. However, any other suitable mechanism mayactuate the jaws. In at least the closed configuration, the jaws 2190may define a volume for holding tissue, and the cooling member 2110 maybe located on an inner tissue interface surface of the jaws 2190. Thejaws 2190 may be actuated to grasp a portion of patient tissue, whichbrings the tissue closer in contact with cooling member 2110.

Although FIGS. 21A and 21B depict a variation in which the set of jawsincludes two jaws 2190, other variations may include three, four, ormore than four jaws 2190. In some variations, the cooling device 2102may include a single set of jaws 2190 and a single cooling member 2110,but in other variations, the cooling device 2102 may include anysuitable number of sets of jaws and/or cooling members. For instance,the cooling device 2102 may include two sets of jaws, each with arespective cooling member, where each jaws and cooling membercombination may be configured to cool a region of tissue overlying arespective target blood vessel.

Methods

Also described herein are methods of using the internal and externalcooling devices described herein to cool adipose tissue overlying atreatment portion of a target blood vessel, which may cause a decreasein the thickness of the adipose tissue layer and improve percutaneousaccess to the target blood vessel. This effect of reduction of adiposetissue, as illustrated in FIG. 4, may occur gradually over a period oftreatment or after treatment. In some variations, the method may be usedto improve access to target blood vessels having fistulas, such as thoseused for facilitating dialysis. In these variations, the coolingtreatment may be carried out after a fistula-formation procedure, or thecooling treatment may be carried out during (i.e., simultaneously with)or before a fistula-formation procedure. In yet other variations, themethod may be used generally to improve access to any target bloodvessel, regardless of whether the target vessel is involved in fistulaformation.

FIG. 23 shows a simplified depiction of the typical vascular anatomy ofthe arm around the elbow that may include one or more target bloodvessels. Specifically, FIG. 23 shows an anterior view of the right arm2301 as would be seen with the palm facing upward. As shown there, thebrachial artery 2300 extends superficially and distally from the upperarm and sinks deeply into the arm near the elbow joint, where thebrachial artery 2300 branches into the radial artery 2302 and the ulnarartery 2304. The upper portion of the ulnar artery 2304 is deeply seatedwithin the arm beneath the superficial flexor muscles (not shown), andleads down the ulnar side of the forearm to the wrist. The anteriorulnar recurrent artery 2306 and the posterior ulnar recurrent artery2308 branches off of the ulnar artery 2304 just below the elbow joint,and these arteries supply blood to the joint and surrounding muscles.Further down the arm, typically just below the radial tuberosity of theradius bone (not shown), the interosseous artery 2309 branches off fromthe ulnar artery 2304 and eventually feeds into the posterior andanterior interosseous arteries (not shown).

Also shown in FIG. 23 are the cephalic vein 2310/2314/2316 and thebasilic vein 2312/2318/2320. The upper cephalic vein 2310 runs along theouter border of the bicep muscle (not shown) continues down into theforearm as lower cephalic vein 2314. The median cephalic vein 2316 joinsthe cephalic vein 2310/2314 near the elbow joint. The upper basilic vein2312 runs along the inner side of the bicep muscle and continues intothe forearm as basilic vein 2320). The lower basilic vein 2320 of thelower arm is sometimes referred to as the common ulnar vein. The mediancubital vein 2318 (in some instances referred to as the median basilicvein) joins the upper basilic vein 2312 and the common ulnar vein 2320.The median cubital vein 2318 and the median cephalic vein 2316 areformed at the branching of the median antebrachial vein 2322. Near thebranching of the median antebrachial vein 2322 into the median cubitalvein 2318 and the medial cephalic vein 2316, a perforating branch 2324connects these vessels with the deep veins of the arm through theantebrachial fascia (not shown).

As shown in FIG. 23, perforating branch 2324 communicates with a firstdeep ulnar vein 2326 and a second deep ulnar vein 2328. These deep ulnarveins 2326/2328 may run substantially parallel on either side of theulnar artery 2304 between the brachial artery 2300 and the interosseousartery 2309, and may branch away from ulnar artery 2304 distal to theinterosseous artery 2309. Between the brachial artery 2300 and theinterosseous artery 2309, the deep ulnar veins 2326/2328 are typicallylocated in close proximity to the ulnar artery 2304, and usually lessthan 2 mm separate the ulnar artery 2304 from the deep ulnar veins2326/2328. Along the length of the deep ulnar veins 2326/2328,transverse branches (not shown) may occasionally connect to the deepulnar veins 2326/2328. Also shown in FIG. 23 are first brachial vein2330 and second brachial vein 2332. The brachial veins 2330/2332generally run along the brachial artery 2300, and the deep ulnar veins2326/2328 feed into the brachial veins 2330/2332 near the elbow joint.Additionally, a pair of radial veins (not shown) may run along theradial artery, and may feed into one or both of the brachial veins.

In some variations, the target blood vessel is a vessel accessed orintended to be accessed for dialysis purposes. Furthermore, the methodmay target multiple blood vessels simultaneously. For example, potentialtarget blood vessels include the cephalic vein (e.g., a forearm segmentor upper arm segment of the cephalic vein) and the basilic vein (e.g., aforearm segment or the median basilic vein segment near the elbow). Thecephalic vein and basilic veins are common sites for arteriovenousfistulas that connect arterial flow to veins. However, the method maytarget other suitable portions of the cephalic vein, the basilic vein,and/or any other blood vessels whose access is obscured by adiposetissue. Vasculature in and around the treatment area of interest,including target blood vessels such as any veins that are arterializedthrough an arteriovenous fistula or any other suitable blood vessels,may be mapped using ultrasound or other suitable modalities prior toand/or during the treatment procedure.

In some variations, the methods of cryolipolysis described herein may beperformed in particular with a surgical procedure to form abrachio-basilic fistula in order to provide a vein having sufficientblood flow necessary for dialysis, but which is otherwise obscured by athick layer of adipose tissue. A method of facilitating percutaneousaccess to a target basilic vein in a patient may begin with applyinglocal anesthesia, general anesthesia or a brachial plexus block to thearm of the patient. Next, a brachio-basilic fistula may be formed in thearm of the patient. The arm may be dissected to provide access to theadipose tissue overlying the target vein. A subcutaneous probe may thenbe inserted into adipose tissue overlying the target vein. Afterinsertion, the probe may be aligned with a treatment portion of thetarget vein. The alignment of the probe may then be verified by eitherfluoroscopy or ultrasound. Additionally or alternatively, an externalcooling member may be provided with a fluidic channel carrying a coolantsubstantially aligned with a treatment portion of the target vein. Asecuring member may be coupled to the cooling member to an externalsurface of the patient.

A selected portion of adipose tissue surrounding the probe may then becooled, thereby forming a depression in the selected portion of adiposetissue overlying the treatment portion of the target vein. The probeand/or the external cooling member may be removed at the end of thecooling treatment period. After a sufficient recovery time has passedfrom the fistula and cryolipolysis procedures, hemodialysis treatmentmay be performed using the basilic vein.

After fistula formation, a recovery time on the order of several weeksor months is common for the fistula to mature. Similarly, the fulleffect of a cryolipolysis procedure may not be evident for about one totwo months. Therefore, fistula formation and cryolipolysis maypreferably be performed together or near in time to each other. In othervariations, cryolipolysis may be performed before or after fistulaformation.

Methods Using Internal Cooling

In some variations described here using internal cooling, the method offacilitating percutaneous access to a target blood vessel in a patientmay include inserting a subcutaneous probe (or other elongate coolingmember) into adipose tissue, aligning the probe with a treatment portionof the target blood vessel, and cooling a selected portion of adiposetissue surrounding the probe, thereby forming a depression in theselected portion of adipose tissue overlying the treatment portion ofthe target blood vessel. The depression may make the treatment portionof the target blood vessel closer to the surface of the skin, which mayease vascular access to that portion of the target blood vessel, sincethe target blood vessel is obscured by less fat. Accordingly, in somevariations, the method may form a depression that is somewhat elongateand is approximately aligned with the treatment portion of the targetblood vessel. In other variations, however, the depression may be alarge general surface area (e.g., an approximate square, circle, or thelike) that includes the area overlying the target blood vessel and more.

Inserting the probe into adipose tissue may comprise inserting a distalend of the probe into the adipose tissue at a first location. The firstlocation may be proximate to (e.g., adjacent to, or otherwise nearby) atreatment portion of the target blood vessel. In some variations, asshown in FIG. 3A, the distal end of the probe remains in direct contactwith the adipose tissue. In these variations, the distal end of theprobe may include the treatment segment configured to cool surroundingadipose tissue. In other variations, as shown in FIG. 3B, the distal endof the probe is passed out of the adipose tissue at a second locationdifferent from the first location. In the variation shown in FIG. 3B,the distal end of the probe may lie external to the patient, while amore proximal segment of the probe includes the treatment segmentconfigured to cool surrounding adipose tissue. Furthermore, in somevariations of the method, multiple probes may be inserted proximate oneor more target blood vessels. For example, multiple probes may beinserted in parallel to simultaneously improve access to multiple targetblood vessels. As another example, multiple probes may be placed inseries in a path approximately tracking the shape of the target bloodvessel, such as to improve access to a curved target blood vessel. Theone or more probes may include any of the various probes describedabove, such as that of FIGS. 3-9, but may additionally or alternativelyinclude any suitable cooling members.

In some variations, the patient skin at the first insertion point (thelocation where the distal end of the probe is inserted) may be puncturedseparately prior to inserting the probe. In these variations, the distalend of the probe may be blunt to help avoid any undesired trauma to theblood vessel or other tissue. For example, the skin may be punctured bya needle, or an incision may be formed to that enable the probe to enterthe adipose tissue. As another example, the skin may be punctured by atrocar or other cannula through which the probe may subsequently enterthe adipose tissue. However, in other variations, the probe may puncturethe skin directly. For example, the probe may include a distal sharpenedend (e.g., a blade) that may or may not be removed from the probe afterthe distal end of the probe is initially inserted into the adiposetissue.

Aligning the probe with a treatment portion of the target blood vesselmay include tracking, within the adipose tissue, the path of at leastthe treatment portion of the target blood vessel. As shown in FIG. 3A,the treatment portion 310 a of the probe may be approximately parallelto the treatment portion of the target blood vessel 60. Depending onfactors such as the size and cooling range of the probe, the probe maybe aligned with the vessel at various depths within the adipose tissue.In one example, the treatment portion of the probe may be aligned withthe blood vessel at a depth approximately halfway between the skin andthe blood vessel. However, the probe may be located below the skin atapproximately one-third of the distance between the skin and the bloodvessel, approximately two-thirds of the distance between the skin andthe blood vessel, or at any suitable depth.

In some variations, aligning the probe may include guiding the depth ofthe probe and/or otherwise orienting the probe. Guiding the depth of theprobe may be performed with the aid of a guide member, such as amagnetic guide member that is external to the patient or internal to thetarget blood vessel and magnetically attracts and/or repels at least aportion of the probe to adjust the depth of the probe in the adiposetissue. Orienting the probe may include adjusting the probe such that aninsulator coupled to the probe is facing any tissue to be protected. Insome variations, viewing radiopaque markers or other markings on theprobe under fluoroscopy or other imaging modalities may help alignand/or orient the probe in the adipose tissue. Additionally oralternatively, probe alignment may be aided with other imagingmodalities to image the probe and/or the target vessel, such asnear-infrared light.

Cooling a selected portion of adipose tissue surrounding the probe maycomprise cooling the probe. In a first variation, cooling the probe maycomprise circulating a coolant in the probe. In some variations, coolingthe probe may include inducing turbulent flow of the coolant. Asdescribed above with reference to internal cooling devices, thecirculated coolant may be a fluid such as liquid or gas. The circulatedcoolant may be repeatedly chilled and delivered to the probe from acooling subsystem, or may originate from a chilled coolant reservoircoupled to the probe. A control subsystem may control the flow rateand/or temperature of the coolant based on the comparison between ameasured probe or coolant temperature and a target probe or coolanttemperature. In some variations, as described above, circulating acoolant in the probe may comprise allowing phase changes in the coolantupon absorbing heat from the surrounding region of adipose tissue (e.g.,allowing liquid coolant to vaporize). After having undergone a phasechange, the warmed coolant may return to a cooling subsystem or bevented outside the probe. In a second variation, cooling the probe maycomprise providing a coolant insert in the form of a solid or semi-solidcoolant in the probe.

Cooling the adipose tissue may be performed in a single session orrepeated in multiple sessions over a treatment period of time.Generally, during each session, the tissue may be cooled for betweenabout 1 minute and about 2 hours. In some variations, in each sessionthe tissue may be cooled for between about 1 hour and about 2 hours. Insome variations, in each session the tissue may be cooled for betweenabout 1 minute and about 30 minutes. In some variations, in each sessionthe tissue may be cooled for between about 1 hour and about 1.5 hours.In some variations, in each session the tissue may be cooled for betweenabout 1.5 hours and about 2 hours. In some variations, in each sessionthe tissue may be cooled for between about 10 minutes and about 20minutes. In some variations, the cooling time for each session may bechosen based on the thickness of the adipose tissue between the skin andthe target vessel. During a treatment session, in some variations all ora portion of the tissue may be cooled to a temperature between about 0°F. and about 40° F. In some variations, all or a portion of the tissuemay be cooled to a temperature between about 5° F. and about 25° F. Insome variations, all or a portion of the tissue may be cooled to atemperature between about 20° F. and about 25° F. In some variations,all or a portion of the tissue may be cooled to a temperature betweenabout 20° F. and about 30° F. Generally, the frequency of the sessionand the duration of the treatment period may depend on the rate oftissue reduction in response to cumulative treatment sessions and/or maydepend on the dimensions of the desired depression or “trench” over thetreatment portion of the target blood vessel. However, generallyspeaking, the treatment period may be between approximately 1 week toapproximately 8 weeks, or approximately 3 weeks to approximately 6weeks. In some variations, the tissue may be treated in a singletreatment session. In some variations, cooling the selected portion ofadipose tissue may allow the skin overlying the depression to lie withinabout 7 millimeters of the treatment portion of the target blood vessel(i.e., the thickness of the layer of adipose tissue between the skin andthe treatment portion of the target blood vessel may be reduced to lessthan or about 7 millimeters). In some variations, cooling the selectedportion of adipose tissue may allow the skin overlying the depression tolie within about 5 millimeters of the treatment portion of the targetblood vessel (i.e., the thickness of the layer of adipose tissue betweenthe skin and the treatment portion of the target blood vessel may bereduced to less than or about 5 millimeters thick). In some variations,this adipose tissue layer thickness may correspond to a desired depth ofthe depression between about 10 millimeters and about 40 millimetersdeep, such as about 25 millimeters deep. In some variations, thedepression may be elongate and track the shape of the treatment portionof the underlying target blood vessel. For example, in these variations,the depression may be between about 80 millimeters and 120 millimeterslong, such as about 100 millimeters long.

In one variation, method of treatment of a patient undergoing abrachio-basilic fistula procedure and cryolipolysis procedure beginswith a determination of the location of a basilic vein. A subcutaneousblunt dissection may then be performed with a surgical tool such as atrocar to access the area of adipose tissue overlying a target basilicvein. A cooling member is then inserted into the adipose tissue. Theposition and location of the inserted cooling member may be verified by,for example, fluoroscopy or ultrasound. For adipose tissue having adepth of 16 mm between the skin and the target blood vessel, thedissection may be performed to insert a cooling member at a depth of 8mm from the skin surface. The cooling member may define a blunt distalportion and have a diameter of 5 mm. The cooling member is cooled for 30minutes at a temperature of 30° F. The above-described process may beperformed under local or general anesthesia, or a brachial plexus block.

Once cryolipolysis treatment is completed, the cooling member isremoved, and the cooling member incision is closed. Thereafter, aprocedure may be performed to form a brachio-basilic fistula. Once thefistula has matured and the targeted area of adipose tissue has receded,access to a target blood vessel is improved, leading to better outcomesfor hemodialysis treatment. Cryolipolysis treatment is not dependent ona particular procedure such as a brachio-basilic fistula procedure andmay be performed separately or in conjunction with other procedures onother target blood vessels.

In some variations, the method may comprise vasoconstricting vasculaturein the skin of the patient overlying the selected portion of adiposetissue and the treatment portion of the target blood vessel.Vasoconstricting the skin vasculature may be performed prior to orsimultaneously with the process of cooling the adipose tissue. In oneexample, vasoconstricting may comprise applying cold therapy to theexternal surface of the skin, such as placing on the skin a cold object(e.g., ice pack or highly thermally conductive metal) that has atemperature cold enough to induce vasoconstriction, but not cold enoughto cause necrosis. In another example, vasoconstricting may compriseapplying a source of positive pressure (e.g., radial compression or aweight) onto the skin. In another example, vasoconstricting may compriseapplying a source of negative pressure (e.g., suction cup with vacuum)onto the skin. In yet another example, vasoconstricting may compriseapplying a vasoconstricting substance, such as epinephrine cream, to theskin. Vasoconstricting may involve any suitable combination ofvasoconstricting processes.

In some variations, the method further includes hydrodissecting theselected portion of adipose tissue overlying the treatment portion ofthe target blood vessel. Hydrodissecting may be performed prior to orsimultaneously with the process of cooling the adipose tissue. In oneexample, hydrodissecting may include injecting saline or anothersuitable fluid into the adipose tissue percutaneously. In anotherexample, hydrodissecting may include introducing saline or anothersuitable fluid through the probe (e.g., through fenestrations in thetreatment segment of the probe). Hydrodissecting the tissue may involveany suitable combination of hydrodissecting processes.

In some variations, the method may comprise agitating the selectedportion of adipose tissue overlying the treatment portion of the targetblood vessel. The agitation may be performed prior to or simultaneouslywith the process of cooling the adipose tissue. The agitation may be amechanical vibration, such an external source (e.g. a vibrating motorplaced on the skin adjacent the adipose tissue to be agitated) or aninternal source (e.g., a vibrating probe). As another example, agitationmay be generated by an external or internal source of acousticvibration. Tissue agitation may involve any suitable combination ofagitation processes.

Methods Using External Cooling

In some variations of methods using external cooling, the method offacilitating percutaneous access to a target blood vessel in a patientincludes providing a cooling member including an elongate fluidicchannel, aligning the fluidic channel with a treatment portion of thetarget blood vessel, coupling the cooling member to an external surfaceof the patient, and cooling a selected portion of adipose tissueoverlying the treatment portion of the target blood vessel, therebyforming a depression in the selected portion of tissue. Similar to thedepressions formed by methods using internal cooling, the depressionformed by external cooling may make the treatment portion of the targetblood vessel closer to the surface of the skin, which may ease vascularaccess to that portion of the target blood vessel, since the targetblood vessel is obscured by less fat. Accordingly, in some variations,the method may form a depression that is somewhat elongate and isapproximately aligned with the treatment portion of the target bloodvessel. In other variations, however, the depression may be a largegeneral surface area (e.g., an approximate square, circle, or the like)that includes the area overlying the target blood vessel.

The provided cooling member may be similar to those described above withrespect to external cooling devices, or may be any suitable coolingmember with a fluidic channel. The cooling member may be attached to thepatient using a securing member (e.g., cuff). In variations in which thecooling member configuration is adjustable relative to the securingmember, the cooling member may be adjusted to align with or track thetarget vessel before the securing member couples the cooling member tothe patient. Alternatively or additionally, such adjustment in alignmentmay be performed while the securing member couples the cooling member tothe patient, and/or after the securing member couples the cooling memberto the patient. In variations in which the securing member is configuredto have variable compressive force, the compressive force on all or aportion of the cooling member may be adjusted before, during, or afterattachment of the cooling member to the patient.

As in the method of using internal cooling, cooling the adipose tissuewith an external cooling device may be performed in a single session orrepeated in multiple sessions over a treatment period of time. In somevariations, the cooling time for each session may be chosen based on thethickness of the adipose tissue between the skin and the target vessel.Furthermore, generally, the frequency of the session and the duration ofthe treatment period may depend on the rate of tissue reduction inresponse to cumulative treatment sessions and/or may depend on thedimensions of the desired depression or “trench” over the treatmentportion of the target blood vessel. Other aspects of the frequency andduration of cooling treatment sessions and treatment period aredescribed in further detail above with respect to methods using internalcooling.

In some variations, the method may comprise vasoconstricting skinvasculature, hydrodissecting adipose tissue overlying the treatmentportion of the target blood vessel, and/or agitating the adipose tissueoverlying the treatment portion of the target blood vessel. Thesevasoconstricting, hydrodissecting, and tissue agitating processes may besimilar to those described above with respect to methods using internalcooling.

It will be understood that the foregoing is only illustrative of theprinciples of the invention, and that various modifications,alterations, and combinations may be made by those skilled in the artwithout departing from the scope and spirit of the invention.Accordingly, the variations of the devices, systems, and methods forinternal and external cooling of adipose tissue can be combined and/orpermutated in any suitable manner.

1. A device for facilitating percutaneous access to a target bloodvessel in a patient, comprising: a subcutaneous probe to carry acoolant, the probe comprising an adipose tissue interface surface and atreatment segment, wherein the treatment segment defines a deliverylumen extending at least the length of the treatment segment to carrythe coolant toward a distal end of the treatment segment and a returnlumen to carry the coolant away from the distal end of the treatmentsegment.
 2. The device of claim 1, wherein the treatment segmentoverlies and is substantially aligned with a treatment portion of thetarget blood vessel.
 3. The device of claim 1, wherein the deliverylumen and the return lumen are in fluid communication with one anotherat the distal end of the treatment segment.
 4. The device of claim 3,wherein at least a portion of the delivery lumen and at least a portionof the return lumen are separated by a porous wall.
 5. The device ofclaim 4, wherein the probe further comprises a valve coupled to thereturn lumen to control a rate of a phase transformation of the coolantacross the porous wall.
 6. The device of claim 1, wherein the probecomprises a proximal probe portion directed along a first axis, andwherein the treatment segment is directed along a second axis that isoriented at a nonzero angle to the first axis.
 7. The device of claim 1,further comprising a temperature sensor coupled to the treatment segmentof the probe that measures at least one of the temperature of thetreatment segment and the temperature of the coolant.
 8. A system forfacilitating percutaneous access to a target blood vessel in a patient,comprising: a cooling device comprising a subcutaneous probe with anadipose tissue interface surface and a treatment segment defining afluidic channel to carry a coolant; and a cooling subsystem comprising acooling mechanism and a fluid distributor, wherein the cooling mechanismmodifies a temperature of the coolant, and the fluid distributordelivers the coolant from the cooling mechanism at a flow rate into thefluidic channel of the probe.
 9. The system of claim 8, wherein thecooling mechanism comprises a closed fluidic system with a heatexchanger.
 10. The system of claim 8, wherein the cooling mechanismcomprises a coolant reservoir in fluid communication with the fluidicchannel.
 11. The system of claim 8, further comprising a controlsubsystem coupled to the cooling subsystem to control at least one ofthe flow rate and the temperature of the coolant.
 12. The system ofclaim 8, further comprising a guide member to reposition the proberelative to a treatment portion of the target blood vessel.